Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs

BACKGROUND: Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia. METHODS: Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, cardiac output, LAD coronary blood flow velocity, and LAD and left circumflex coronary artery subendocardial segment length. Regional myocardial contractility was evaluated with the slope of the preload recruitable stroke work relationship determined from a series of left ventricular pressure-segment length diagrams in the LAD and left circumflex coronary artery zones. Diastolic function was assessed with a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity in LAD and left circumflex coronary artery regions, and regional chamber stiffness constants derived using monoexponential and three-element exponential curve fitting in each zone. On separate experimental days, hemodynamics and indices of regional functional were obtained in the conscious state and during 1.1 and 1.6 minimum alveolar concentration end-tidal desflurane or isoflurane before and during LAD occlusion. RESULTS: In conscious dogs, LAD occlusion abolished regional stroke work, increased chamber stiffness (monoexponential: 0.39 +/- 0.04 during control to 1.34 +/- 0.39 mm-1 during LAD occlusion), and decreased the rate of early ventricular filling in the ischemic zone. These changes were accompanied by increased contractility (slope: 103 +/- 8 during control to 112 +/- 7 mmHg during LAD occlusion), rapid filling rate (maximum segment lengthening velocity: 46 +/- 5 during control to 55 +/- 7 mm.s-1 during LAD occlusion), and chamber stiffness (monoexponential: 0.43 +/- 0.05 during control to 1.14 +/- 0.25 mm-1 during LAD occlusion) in the normal region. Increases in tau were also observed in the conscious state during the period of myocardial ischemia. Desflurane and isoflurane increased tau and decreased the slope and maximum segment lengthening velocity in a dose-related manner. Monoexponential and three-element element exponential curve fitting were unchanged by the volatile anesthetics in the absence of ischemia. Myocardial contractility and rapid filling rate were enhanced in the nonischemic region during LAD occlusion in the presence of desflurane and isoflurane. In contrast to the findings in the conscious state, ischemia-induced increases in tau and chamber stiffness in the ischemic and normal zones were attenuated during anesthesia induced by desflurane and isoflurane. CONCLUSIONS: The results indicate that increases in contractility of remote myocardium during brief regional ischemia were preserved in the presence of desflurane and isoflurane anesthesia. In addition, desflurane and isoflurane blunted ischemia-induced increases in tau and regional chamber stiffness in both the ischemic and nonischemic zones. These results demonstrate that the volatile anesthetics may exert important beneficial actions on left ventricular mechanics in the presence of severe abnormalities in systolic and diastolic function during ischemia.     

Regional vasodilating properties of isoflurane in normal swine myocardium

BACKGROUND: Studies of the coronary vasodilating properties of isoflurane have produced inconsistent results. Isoflurane has been reported to cause minimal or no coronary vasodilation, mild dose-related vasodilation, or even near-maximal coronary vasodilation. The current study was performed to clarify the direct coronary vasodilating potency of isoflurane. METHODS: We determined the vasodilating properties of isoflurane in regionally perfused swine myocardium. Six domestic swine were anesthetized with pentobarbital and fentanyl. The left anterior descending artery (LAD) was cannulated and perfused with blood drawn from the carotid artery and passed thorough a membrane oxygenator. LAD arterial flow was controlled by a calibrated roller pump with continuous digital readout, and LAD arterial pressure was measured directly. The anterior interventricular vein was cannulated and dimension crystals placed in the LAD-perfused myocardium. The vasodilation response to 0, 1, 2, and 3% isoflurane administered via the membrane oxygenator was determined and compared to maximal vasodilation produced by regional intracoronary administration of adenosine. RESULTS: Systemic blood pressure and heart rate remained constant throughout the experiment. With 3% isoflurane, systolic shortening and regional myocardial oxygen consumption decreased by 60 and 20%, respectively. The same concentration increased coronary blood flow by 51 +/- 34% and reduced coronary vascular resistance by 32.9 +/- 11.0%. Neither coronary blood flow nor coronary vascular resistance was affected with 1% isoflurane. Regional coronary administration of adenosine produced much greater changes in both coronary blood flow (+591%) and coronary vascular resistance (-92.5%). Isoflurane increased the venous oxygen content of the anterior interventricular vein in a dose-dependent fashion from 4.85 vol% at control to 6.17, 7.01, and 8.63 vol% at 1, 2, and 3% isoflurane, respectively. CONCLUSIONS: We conclude that isoflurane is a mild dose-dependent coronary vasodilator. At a 1% concentration, the coronary vasodilating properties of isoflurane are minimal.     

Effects of intraaortic balloon pumping on septal arterial blood flow velocity waveform during severe left main coronary artery stenosis

OBJECTIVES: We sought to evaluate the effect of intraaortic balloon pumping on the phasic blood velocity waveform into myocardium with severe coronary artery stenosis. BACKGROUND: In the presence of severe coronary artery stenosis, it is not clear whether intraaortic balloon pumping augments intramyocardial inflow during diastole or changes systolic retrograde blood flow from the myocardium to the extramural coronary arteries. METHODS: Using anesthetized open chest dogs (n=7), we introduced severe stenosis in the left main coronary artery to reduce the poststenotic pressure to approximately 60 mm Hg (>90% diameter stenosis). Septal arterial blood flow velocities were measured with a 20-MHz, 80-channel ultrasound pulsed Doppler velocimeter. Left anterior descending arterial flow, aortic pressure and poststenotic distal coronary pressure were measured simultaneously. The diastolic anterograde flow integral and systolic retrograde flow integral were compared in the presence and absence of intraaortic balloon pumping. RESULTS: Although intraaortic balloon pumping augmented diastolic aortic pressure, this pressure increase was not effectively transmitted through stenosis. Septal arterial diastolic flow velocity was not augmented, and left anterior descending arterial flow was unchanged during intraaortic balloon pumping. CONCLUSIONS: In the presence of severe coronary artery stenosis, intraaortic balloon pumping failed to increase diastolic inflow in the myocardium and did not enhance systolic retrograde flow from the myocardium to the extramural coronary artery. Thus, the major effect of intraaortic balloon pumping on the ischemic heart with severe coronary artery stenosis may be achieved by reducing oxygen demand by systolic unloading.     

Perfusion of ischemic myocardium during anesthesia with sevoflurane

BACKGROUND: Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. METHODS: Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. RESULTS: Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. CONCLUSIONS: The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.     

Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography

BACKGROUND: Coronary flow reserve has been considered an important diagnostic index of the functional significance of coronary artery stenosis. With Doppler technique, it has been assessed as the ratio of hyperemic to basal coronary flow velocity (coronary flow velocity reserve [CFVR]) by invasive or semiinvasive methods with a Doppler catheter, a Doppler guide wire, and a transesophageal Doppler echocardiographic probe. Recent technological advancement in transthoracic Doppler echocardiography (TTDE) provides measurement of coronary flow velocity in the distal portion of the left anterior descending coronary artery (LAD) and may be useful in the noninvasive CFVR measurement. The purpose of this study was to evaluate the value of CFVR determined by TTDE for the assessment of significant LAD stenosis. METHODS AND RESULTS: We studied 36 patients who underwent coronary angiography for the assessment of coronary artery disease. The study population consisted of 12 patients with significant LAD stenosis (group A) and 24 patients without significant LAD stenosis (group B). With TTDE, coronary flow velocities in the distal LAD were recorded at rest and during hyperemia induced by intravenous infusion of adenosine (0.14 mg x kg(-1) x min(-1)) under the guidance of color Doppler flow mapping. Adequate spectral Doppler recordings of coronary flow in the distal LAD for the assessment of CFVR were obtained in 34 of 36 study patients (94%). The peak and mean diastolic coronary flow velocities at baseline did not differ between groups A and B (23.6+/-10.3 versus 22.9+/-6.6 cm/s and 16.4+/-8.6 versus 14.5+/-4.0 cm/s, respectively). However, the peak and mean coronary flow velocities during hyperemia in group A were significantly smaller than those in group B (35.6+/-16.3 versus 54.2+/-16.3 cm/s and 24.7+/-13.1 versus 37.9+/-13.0 cm/s, respectively; P<.01). There were significant differences in CFVR obtained from peak and mean diastolic velocity between groups A and B (1.5+/-0.2 versus 2.4+/-0.4 and 1.5+/-0.2 versus 2.6+/-0.4, respectively; P<.001). A CFVR from peak diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 82% for the presence of significant LAD stenosis. A CFVR from mean diastolic velocity <2.0 had a sensitivity of 92% and a specificity of 86% for the presence of significant LAD stenosis. CONCLUSIONS: CFVR determined by TTDE is useful in the noninvasive assessment of significant stenotic lesion in the LAD.     

New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo Doppler

BACKGROUND: We tested the hypothesis that blood flow velocity could be recorded in the left anterior descending coronary artery (LAD) during transthoracic echocardiography by use of second harmonic echo Doppler modality along with contrast enhancement (intravenous Levovist) at rest and after pharmacologically induced maximal vasodilation to assess coronary flow reserve (CFR) with a totally noninvasive approach. METHODS AND RESULTS: Fifty-six consecutive patients undergoing coronary angiography underwent transthoracic contrast-enhanced pulsed-wave Doppler recording of blood flow velocity in the LAD by use of harmonic color Doppler as a guide at rest and after maximal vasodilation by dipyridamole infusion. Contrast enhancement with the harmonic mode greatly improved the success rate of recording adequate pulsed-wave Doppler signal in the LAD. CFR was (mean+/-SD) 1.54+/-0.7 in patients with (group 1) and 2. 79+/-0.9 in patients without (group 2) significant LAD stenosis (lumen narrowing >70%) (P<0.001); sensitivity and specificity in detecting significant LAD stenosis were 86% and 90%, respectively. There was close agreement between CFRs determined by this new method and intracoronary Doppler flow wire. CONCLUSIONS: Contrast-enhanced transthoracic echo Doppler with the harmonic mode is a feasible and promising technique for assessing CFR in a totally noninvasive way.     

In vivo observation of subendocardial microvessels of the beating porcine heart using a needle-probe videomicroscope with a CCD camera

We developed a portable needle-probe videomicroscope with a charge-coupled device (CCD) camera to visualize the subendocardial microcirculation. In 12 open-chest anesthetized pigs, the sheathed needle probe with a doughnut-shaped balloon and a microtube for flushing away the intervening blood was introduced into the left ventricle through an incision in the left atrial appendage via the mitral valve. Images of the subendocardial microcirculation of the beating heart magnified by 200 or 400 on a 15-in. monitor were obtained. The phasic diameter change in subendocardial arterioles during cardiac cycle was from 114 +/- 46 microns (mean +/- SD) in end diastole to 84 +/- 26 microns in end systole (p < 0.001, n = 13, ratio of change = 24%) and that in venules from 134 +/- 60 microns to 109 +/- 45 microns (p < 0.001, n = 15, ratio of change = 17%). In contrast, the diameter of subepicardial arterioles was almost unchanged (2% decrease, n = 5, p < 0.01), and the venular diameter increased by 19% (n = 8, p < 0.001) from end diastole to end systole. Partial kinking and/or pinching of vessels was observed in some segments of subendocardial arterioles and venules. The percentage of systolic decrease in the diameter from diastole in the larger (> 100 microns) subendocardial arterioles and venules was greater than smaller (50-100 microns) vessels (both p < 0.05). In conclusion, using a newly developed microscope system, we were able to observe the subendocardial vessels in diastole and systole.(ABSTRACT TRUNCATED AT 250 WORDS)     

Halothane and the reperfusion injury in the intact animal model

We studied the effect of halothane on regional myocardial function during acute ischemia and reperfusion in an open-chest pig model. Anesthesia was induced with thiopental and fentanyl and maintained with an intravenous (IV) infusion of pentobarbital and fentanyl. Regional myocardial function was studied with microsonometers placed in the subendocardium supplied by the left anterior descending coronary (LAD) and circumflex coronary artery (LX). Systolic function was evaluated with reference to the end-systolic pressure-length relationship (ESPLR) and regional systolic shortening. Diastolic dysfunction was studied with postsystolic shortening (PSS). Ischemia was induced with 15 min of total occlusion of the LAD artery, and thereafter reperfusion was allowed for 120 min. Five groups were studied: one group received only pentobarbital and fentanyl (n = 10); the other groups received halothane 0.2% (n = 5), 0.4% (n = 7), 0.6% (n = 5), and 0.8% (n = 5). The pentobarbital and fentanyl infusion was adjusted in the halothane groups in an effort to maintain arterial blood pressure and heart rate within specified limits (when possible). Results indicate that regional dysfunction during acute ischemia was equal among all the groups. However, on reperfusion, halothane significantly reduced the incidence of ventricular arrhythmias. Halothane (0.6% and 0.8%) was associated with less regional postischemic systolic dysfunction during reperfusion when compared to the other groups. Hearts subjected to 0.6% and 0.8% halothane also were less stiff at the end of systole (i.e., the extrapolated ventricular volume at zero ventricular pressure was less) after 120 min reperfusion compared to animals receiving less halothane. However, diastolic dysfunction was equal among the groups during reperfusion. We conclude that, in this model, administration of halothane is associated with improved recovery of regional systolic function and potentially beneficial pressure-length relations at the end of systole after acute severe myocardial ischemia and reperfusion. Furthermore, administration of halothane was associated with fewer reperfusion arrhythmias compared to animals not receiving halothane.     

Intrathecal neostigmine, but not sympathectomy, relieves mechanical allodynia in a rat model of neuropathic pain

OBJECTIVE: In myocardial ischaemia, slow conducting capsaicin-sensitive C-fibres are activated. Apart from the mediation of pain, activation of these fibres causes release of various peptides, such as calcitonin gene-related peptide (CGRP), which is a potent vasodilator. The aim of this study was to investigate the role of CGRP in the context of myocardial ischaemia in vivo. METHODS: The left anterior descending coronary artery (LAD) was occluded during 45 min in 27 anaesthetised open-chest pigs. LAD flow, mean arterial pressure (MAP), heart rate, peak dP/dt, arterial and coronary venous concentration of CGRP was measured prior to ischaemia, and during 4 h of reperfusion. The extent of myocardial infarction was measured using staining with triphenyl tetrazolium chloride. RESULTS: Retroinfusion of CGRP (100 micrograms) into the ischaemic myocardium was associated with a more pronounced hyperaemia, and systemic hypotension, during early reperfusion. The infarct size in relation to the area at risk was not affected by CGRP or the CGRP antagonist CGRP(8-37), and averaged 67 +/- 3%. There were no changes in plasma CGRP levels during ischaemia or reperfusion. CONCLUSION: Exogenously administered CGRP can cause systemic hypotension and augments postischaemic coronary flow. In this model, no cardioprotective effect of CGRP could be proven.     

Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography

OBJECTIVES: This study was designed to examine the effects of a beta-adrenergic blocking agent on the ischemic response to dobutamine stress and to determine the degree to which these effects can be abolished by the addition of atropine. BACKGROUND: Whether beta-blockade affects the sensitivity of dobutamine stress echocardiography for the diagnosis of coronary artery disease has been controversial. METHODS: In nine pigs, a left anterior descending coronary artery stenosis was created to reduce flow reserve (maximal/rest flow) to 1.1 to 1.9 without baseline regional wall motion abnormalities. This corresponded to a 50% to 90% diameter stenosis. Wall thickening was measured using epicardial echocardiography. Regional lactate production and coronary venous pH were monitored from an adjacent cardiac vein. A standard protocol of dobutamine stress echocardiography was first performed. After normalization of the ischemic abnormalities elicited with this infusion, esmolol was infused at 50 micrograms/kg body weight per min and the dobutamine test was repeated, with 1.0 mg of atropine added at the maximal dobutamine dose. RESULTS: Without esmolol, dobutamine stress induced myocardial ischemia with a reduction in regional wall thickening and lactate production in all nine pigs. Multiple regression analysis revealed that coronary flow per heartbeat (p < 0.01) and lactate production (p < 0.05) independently correlated with regional wall thickening during dobutamine stress. The beta-blocker significantly reduced heart rate and regional oxygen consumption and altered the relation between coronary flow per heartbeat and regional wall thickening (p < 0.05) during dobutamine stress. Esmolol prevented dobutamine-induced ischemia (lactate production and wall motion abnormalities) in seven of nine pigs. The addition of atropine induced lactate production and a reduction in wall thickening in five of seven pigs in which ischemia had been prevented by beta-blockade. However, lactate production was higher and regional venous pH was lower with the baseline dobutamine infusion than with that performed after esmolol with atropine added at the maximal dobutamine dose (p < 0.05). CONCLUSIONS: A correlation between regional wall thickening and coronary flow per heartbeat was demonstrated during baseline dobutamine stress. Beta-blockade shifted this relation so that dobutamine stress-induced myocardial ischemia was attenuated. The mechanisms by which beta-blockade prevents dobutamine-induced ischemia appeared to be mainly through decreases in heart rate and rate of rise in left ventricular pressure, improvement of regional coronary flow per heartbeat and attenuation of regional ischemic lactate production. Adding atropine in conventional doses enhanced the ability of dobutamine stress to induce myocardial ischemia but did not completely abolish the effects of beta-blockade on either the severity of dobutamine-induced wall thickening abnormalities or regional metabolic disturbances.     

Comparison between thallium-201 and technetium-99m-tetrofosmin uptake with sustained low flow and profound systolic dysfunction

Technetium-99m-tetrofosmin uptake was compared to that of 201Tl in the setting of low flow and systolic dysfunction. METHODS: In nine open-chested dogs, a severe left anterior descending (LAD) coronary artery stenosis resulted in a 54.3% mean flow reduction and decreased left ventricular thickening from 21% +/- 1% to -3 +/- 2%. After 30 min, 37 MBq (1 mCi) of 201Tl and microspheres were injected and initial and 2-hr redistribution images acquired. Two hours later, 370 MBq (10 mCi) of 99mTc-tetrofosmin and microspheres were injected and an image was obtained. LAD: left circumflex (LCX) count ratios for both tracers and flows were calculated by well counting postmortem, and 201Tl and 99mTc-tetrofosmin defect magnitudes were determined by quantitative image analysis. RESULTS: LAD:LCx flow ratios were similar during 201Tl and 99mTc-tetrofosmin injections (0.48 +/- 0.04 versus 0.49 +/- 0.05, p = n.s.). Final 201Tl activity (0.66 +/- 0.04) was significantly higher than 99mTc-tetrofosmin (0.55 +/- 0.05; p < 0.05). LAD/LCx 99mTc-tetrofosmin image defect count ratio was similar to 201Tl defect count ratio on the initial rest 201Tl scan (0.57 +/- 0.03 versus 0.56 +/- 0.02, p = ns), but significantly less than 201Tl defect count ratio at 2 hr (0.57 +/- 0.03 versus 0.65 +/- 0.02, p < 0.05). CONCLUSION: In a low-flow model with profound systolic dysfunction, myocardial 99mTc-tetrofosmin uptake ( > 50%) reflective of viability was observed in the asynergic zone perfused by the stenotic LAD.     

18F-2-deoxyglucose deposition and regional flow in pigs with chronically dysfunctional myocardium. Evidence for transmural variations in chronic hibernating myocardium

BACKGROUND: Hibernating myocardium in patients with collateral-dependent myocardium is characterized by relative reductions in resting flow and increases in the uptake of 18F-2-deoxyglucose (FDG) in the fasting state. We performed the present study to examine whether these key physiological alterations could be produced in a porcine model of chronic coronary occlusion and to assess whether the adaptations consistent with hibernation varied across the myocardial wall. METHODS AND RESULTS: We chronically instrumented pigs (n = 18) with a fixed occluder on the proximal left anterior descending coronary artery (LAD). Three months later, ventricular function, regional myocardial perfusion, and FDG deposition (by excised tissue counting or positron emission tomography) were assessed in pigs after an over-night fast in the closed-chest anesthetized state. Total LAD occlusion with angiographic collaterals was present in the majority of animals. Left ventriculography showed severe anterior hypokinesis, and resting perfusion was significantly reduced in the hibernating LAD region in comparison with the normal remote regions (subendocardium: 0.80 +/- 0.06 versus 1.07 +/- 0.06 mL.min-1.g-1, P < .001; full-thickness: 0.87 +/- 0.04 versus 0.99 +/- 0.06 mL.min-1.g-1, P < .01). There was a twofold increase in full-thickness fasting FDG uptake in the dysfunctional LAD region (1.8 +/- 0.2 by positron emission tomography versus 1.9 +/- 0.1 by ex vivo counting). Ex vivo tissue counting revealed a pronounced transmural variation in FDG uptake in the hibernating region (LAD/normal), which averaged 2.5 +/- 0.2 in the subendocardium, 1.9 +/- 0.2 in the midmyocardium, and 1.4 +/- 0.1 in the subepicardium. CONCLUSIONS: These results demonstrate that pigs instrumented with a proximal LAD stenosis develop hibernating myocardium characterized by relative reductions in resting function and perfusion in association with increased uptake of FDG in the fasting state. The transmural variations in relative resting flow and FDG uptake suggest that myocardial adaptations consistent with hibernation are most pronounced in the subendocardial layers and vary in relation to local coronary flow reserve.     

Working Group Report 2: In situ caries models, saliva, microbiology, and statistical considerations

We present a case of a single coronary artery where the right coronary artery (RCA) arose from its proximal part. This rare anomaly was detected during elective coronary angiography in a patient with suspected coronary artery disease. The single coronary artery originated from the left sinus of valsalva, giving rise to RCA proximally and distally dividing into left anterior descending (LAD), ramus intermedius and left circumflex (LCX) arteries. The anginal symptoms in this patient was attributed to a significant stenosis at the proximal LAD which was subsequently dilated by coronary angioplasty. To the best of our knowledge, this is the first reported case of angioplasty of LAD in an anomalous single coronary artery.     

Interventricular septal motion in patients with proximal and distal left anterior descending coronary artery lesions

In order to evaluate the ability of the echocardiogram to detect and localize left main or left anterior descending (LAD) coronary artery lesions, 43 patients were studied. The systolic excursion of the left side of the septum and the ratio of posterior wall to septal excursion were measured. Seventeen patients had no LAD lesions; all had systolic septal excursion of 3 mm or greater. Twelve patients with septal excursion of 2 mm or less all had left main or LAD lesions, but 14 other patients with LAD lesions had septal excursions of 3 mm or greater. Nine of 16 patients with LAD lesions proximal to the first septal branch had reduced or absent septal excursion, as did three of ten with LAD lesions distal to the first septal branch. In a setting of coronary artery disease reduced or absent septal motion on echocardiography suggests involvement of the left main or left anterior descending coronary. However, the technique is relatively insensitive, with 54% of the LAD patients having normal septal motion.     

Angina pectoris caused by coronary microvascular spasm

BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest. METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein. FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm. INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.     

Abnormal coronary flow dynamics at rest and during tachycardia associated with impaired left ventricular relaxation in humans: implication for tachycardia-induced myocardial ischemia

OBJECTIVES: This study attempted to clarify the effect of ventricular relaxation abnormalities on coronary flow dynamics at rest and during tachycardia in humans. BACKGROUND: Ventricular relaxation abnormality has been demonstrated in animals to have an adverse impact on early diastolic coronary flow dynamics. However, this relation has not been established in humans. Even if the adverse effect were latent at rest, it might become evident during tachycardia because tachycardia reduces coronary flow reserve and facilitates the production of myocardial ischemia. METHODS: Doppler phasic left coronary flow velocity pattern was obtained at rest and during tachycardia in 23 patients without coronary stenosis. The time constant of left ventricular isovolumic pressure (tau) was used to assess ventricular relaxation. RESULTS: The time to peak flow velocity of the diastolic coronary flow wave was longer, and the fraction of the first third of diastolic coronary flow was smaller, in patients with a longer tau (r = 0.58, p < 0.01; r = -0.44, p < 0.05), indicating a close relation between early diastolic coronary flow dynamics and ventricular relaxation. Although rapid atrial pacing yielded an increase in the coronary flow velocity integral per minute in all patients, diastolic coronary flow velocity integral per minute increased in 9 patients with a normal (< or = 40 ms) tau at rest but decreased in 14 patients with a longer (> 40 ms) tau at rest. CONCLUSIONS: Impaired left ventricular relaxation was associated with decreased coronary flow in early diastole at rest and decreased coronary flow throughout diastole during tachycardia in patients without coronary stenosis. These findings may provide more insight into the mechanism of tachycardia-induced subendocardial ischemia in patients with impaired ventricular relaxation but without concomitant coronary stenosis.     

Effects of halothane on global and regional biventricular performances and on coronary hemodynamics before and during right coronary artery stenosis in the dog

BACKGROUND: Previously, it was suggested that right ventricular (RV) free wall dysfunction does not necessarily elicit global hemodynamic alterations. This was investigated in a canine model of halothane-induced right coronary artery (RCA) insufficiency. METHODS: Two concentrations (0.8% and 1.6% end tidal) of halothane on global and regional RV and left ventricular (LV) performance and on coronary, pulmonary, and systemic hemodynamics were studied in 10 open-chest dogs first before and, subsequently, during critical RCA stenosis. RESULTS: In the absence of stenosis, halothane caused progressive and comparable depression of regional and global RV and LV function and reduction of RCA flow. Halothane administered during RCA stenosis caused disproportionate decreases in RCA flow and segment shortening and increases in systolic segment lengths in the area supplied by the stenosed RCA that were approximately twice as great as before stenosis. Such severe regional RV dysfunction was not accompanied by greater depression of global RV and LV pump function (systolic pressures and stroke volume). CONCLUSIONS: In the canine heart with its dominant left coronary system, RCA insufficiency (on the basis of halothane-induced hypotension) caused regional RV dysfunction suggesting ischemia that was not accompanied by global hemodynamic alteration.     

A noninjury, diet-induced swine model of atherosclerosis for cardiovascular-interventional research

To investigate whether atherosclerotic vascular disease in the microswine model can be induced by atherogenic diet alone and does not require balloon injury or endothelial denudation as widely stated in the literature, 28 female Yucatan microswine were fed a high-fat, high-cholesterol diet, including 2% sodium cholate, for an average of 310 +/- 13 days. Four control swine were placed on a regular diet for an average of 287.2 +/- 7.8 days. Selective coronary arteriography and morphologic and histologic studies were performed at the end of this period. Coronary arteries were fixed in vivo by pressure perfusion of formalin. Angiograms and sequential histologic sections were reviewed by a double-blind team. The angiography did not show apparent disease in all vessels but generally revealed mild irregularity. Quantitatively, there was a 30.5 +/- 3.5% stenosis (mean +/- standard error, P < 0.05 vs. control) in left anterior descending (LAD), 40.7 +/- 4.5% of stenosis in right coronary artery (RCA) (P < 0.01 vs. control), and 24.8 +/- 3.7% of stenosis in left circumflex artery (LCX). The lesions were eccentric in 95% of LCA, 95.8% of RCA, and 75% of LCX, and the remainder were concentric lesions. Typical lesions were characterized by significant intimal proliferation, cholesterol clefts, necrotic cores, heavy extracellular fat deposition, and calcification. Control animals had only occasional, minimal intimal lipid deposition in coronary arteries. These findings suggest that the Yucatan microswine is an ideal coronary atherosclerosis animal model for vascular research. Lesions can be induced by atherogenic diet alone. Cholesterol uptake is increased by adding sodium cholate to the feed. Moreover, balloon injury of the intima or media is not required to induce significant atherosclerotic lesions in coronary arteries.     

Rapid genomic changes in newly synthesized amphiploids of Triticum and Aegilops. II. Changes in low-copy coding DNA sequences

Postischemic myocardium possesses considerable contractile and metabolic reserves, but their mobilization could result in increased cell death. We tested the hypothesis that beta-adrenergic stimulation of reperfused myocardium would increase segment work more than O2 consumption, thereby improving efficiency without increased cell death. In 16 open-chest anesthetized dogs, the left anterior descending coronary artery (LAD) was ligated for 2 h; during the reperfusion period, isoproterenol (ISO; 0.1 microg/kg/min, i.v.) was administered to nine of the animals. Regional myocardial segment length and force were measured in the anterior (LAD) and posterior circumflex coronary artery (CFX) regions of the left ventricular myocardium. Work was calculated as the integrated products of force and shortening for each region. Regional myocardial O2 consumption was obtained from LAD flow and arterial and local venous O2 saturations. Infarct size (tetrazolium) was measured in the treated and untreated hearts at the end of the experiment. In untreated hearts, the first derivative of left ventricular pressure, cardiac output, and external work were significantly depressed during reperfusion; ISO restored all values to preocclusion levels. Regional myocardial work in both LAD and CFX regions was significantly increased by ISO (from 564 +/- 207 to 1,635 +/- 543 g/mm/min in LAD, and from 753 +/- 90 to 1,426 +/- 245 g/mm/min in CFX). Efficiency (work/oxygen consumption) of the reperfused region was similarly increased. LAD flow was significantly increased by ISO, and O2 extraction was unchanged. Infarct size was 28.2 +/- 4.7% in untreated hearts and 29.0 +/- 3.5% in ISO hearts. Thus isoproterenol stimulation significantly improved both regional and global function without subsequent evidence of increased cell death.     

Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat

OBJECTIVE: The aim was to investigate the phasic characteristics of normal human left coronary artery flow and velocity profiles across the vessel. METHODS: The phasic characteristics of flow in the human left anterior descending coronary artery, the centreline flow velocities, and the velocity profiles were measured in 10 patients during corrective surgery for atrial septal defect after closure of the defect. None of these patients had any detectable coronary artery stenosis or left ventricular hypertrophy. Measurements were made with a 20 MHz 80 channel pulsed Doppler velocimeter. RESULTS: The velocity waveform displayed a diastolic-predominant pattern with a systolic to diastolic velocity ratio of 0.29(SD 0.17). Reverse flow was observed in early systole in five patients and in mid to late systole in six patients. The values of peak Reynolds number, unsteadiness parameter, and pulsatility index were 504(198), 2.5(0.6), and 5.9(4.4) respectively. The velocity profiles during diastole showed considerable variability in shape, ranging from symmetrical to skewed to M shaped patterns. The peak wall shear rate was 765(250) s-1 on the epicardial wall of the vessel and 712(301) s-1 on the myocardial wall; the difference was not statistically significant. CONCLUSIONS: The velocity waveform displayed a diastolic-predominant pattern. Considerable variability in shape of the velocity profile was found and was perhaps due to the time evolution of the velocity profile within the diastolic time period.