Effects of pulsatile and nonpulsatile coronary perfusion on performance of the canine left ventricle

This study compares the effect of pulsatile (Group C, Fib/P) and nonpulsatile (Group B, Fib/NP) coronary perfusion on myocardial performance during 2 hours of normothermic ventricular fibrillation. Group A (BH/NP), used as a base-line observation, consisted of 2 hours of nonpulsatile coronary perfusion in beating hearts. The assessment of ventricular performance included diastolic ventricular compliance, myocardial oxygen consumption and lactate extraction, regional myocardial blood flow, and histology. After 120 minutes of ventricular fibrillation, Group C showed normal ventricular diastolic compliance as compared to a 50 per cent decrease in Group B (p less than 0.01). Myocardial oxygen consumption was not significantly different from that in Group B. Because of a 70 per cent increase in oxygen extraction above Group B (p less than 0.05), total left ventricular myocardial blood flow was reduced (103 +/- 23 versus 260 +/- 36 ml. per 100 Gm. per minute, p less than 0.05) and had near-constant resistance. Lactate extraction was significantly greater and more stable as compared to Group B (9.28 +/- 1.33 versus 1.8 +/- 1.08, p less than 0.05). Left ventricular endocardial/epicardial flow ratio was greater in Group C (1.21 +/- 0.08 versus 1.06 +/- 0.06, p less than 0.05). Minimal subendocardial histologic changes were present as compared to the marked patchy subendocardial ischemic changes seen in Group B. The results demonstrate that the addition of pulsatile flow to coronary perfusion minimized the deleterious effects of prolonged ventricular fibrillation on myocardial performance.     

Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle

OBJECTIVE: Thyroid hormone modifies cardiac action potentials and outward potassium currents directly and indirectly e.g. through beta-adrenergic signaling pathway. We thus examined the expression of six voltage-gated potassium channel alpha-subunits in the rat left ventricle under hypo- and hyperthyroid status, and tested roles of beta-adrenergic signaling pathway in their expressions under both status. METHODS: Hypothyroidism and hyperthyroidism were induced by administration of methimazole (MMI) for 4 weeks and by injection of L-thyroxine (T4) to the MMI-treated rats for the last 7 days, respectively. To distinguish the effects of T4 and the beta-adrenergic system, propranolol (Pro) was administered to the MMI-treated rats together with T4, and isoproterenol (Iso) was injected to MMI-treated rats for the last 7 days. The mRNA levels of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 in the left ventricles were determined by ribonuclease protection assay. RESULTS: MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05). T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05). Kv4.2 mRNA level was restored to the control level by T4. In contrast, the Kv1.2 and Kv1.4 mRNA levels increased in hypothyroid rats (161% and 186% of control value, respectively; n = 6, p < 0.01) and decreased in hyperthyroid rats (14% and 33% of control value, respectively; n = 6, p < 0.01). The Kv4.3 mRNA level was not altered by thyroid status. Pro did not inhibit the T4-induced hypertrophy. Iso induced cardiac hypertrophy. Pro or Iso by itself did not alter Kv mRNA levels except for Kv1.2, the message of which was decreased by Iso. CONCLUSION: Thyroid hormone differentially regulates the expression of Kv1.4, Kv1.5, Kv2.1 and Kv4.2 mRNA levels in the rat left ventricle. This effect is not mediated through beta-adrenergic signaling pathway. On the other hand, the reduction in Kv1.2 mRNA level was associated with cardiac hypertrophy induced by T4 or Iso.     

Chronic total occlusion of the left main coronary artery

Total chronic occlusion of the left main coronary artery is a rare angiographic finding in a catheterization laboratory. After reviewing the coronary angiographies performed in our laboratory between 1986 to 1995, we found a prevalence of 0.04%. These patients presented unspecific symptoms similar to other kinds of coronary artery disease. In all cases, the right coronary artery was dominant with extensive collateral circulation to the left coronary artery. Ventricular function was normal in 50% of the cases. Probably, in these unusual cases, the best therapeutic approach is surgical revascularization.     

Total occlusion of the left common coronary artery--a case report

Total chronic occlusion of the left main coronary artery is an unusual finding. After a review of the literature, the authors present a case report of a patient with stable angina and total occlusion of the left main coronary artery, right coronary with atherosclerotic lesions and normal ventricular function.     

Complete occlusion of the left main coronary artery and the importance of coronary collateral circulation

Study of four patients who survived complete occlusion of the left main coronary artery forms the basis of conclusions concerning the functional significance of coronary collateral circulation. Each of these patients had prominent collateral circulation from the right coronary artery. Global left ventricular function was maintained to the extent that congestive heart failure did not occur; the biplane ejection fraction was normal in the two patients where measurement was possible. The peak rate of systolic wall thickening by roentgen videometry in anterior left ventricular segments was normal in one patient and mild to moderately depressed in another. Experience with the patients described herein indicates that coronary collateral flow can provide critically needed circulatory support for the patient with coronary artery disease.     

False aneurysm of the left ventricle and coronary aneurysms in Beh?et disease

A false left ventricular aneurysm and coronary artery aneurysm were discovered in a 29 year old patient with Beh?et's syndrome. The operation under cardiopulmonary bypass consisted of closing the neck of the false aneurysm by an endo-aneurysmal approach with a Gore-Tex patch. The coronary artery aneurysms were respected. There were no postoperative complications. Cardiac involvement is rare in Beh?et's syndrome (6%). The originality of this case is the association of two aneurysmal pathologies: the coronary and ventricular aneurysms due to the angiitis and the myocardial fragility induced by ischaemia.     

Effects of hypertrophy on regional action potential characteristics in the rat left ventricle: a cellular basis for T-wave inversion?

BACKGROUND: In cardiac hypertrophy, ECG T-wave changes imply an abnormal sequence of ventricular repolarization. We investigated the hypothesis that this is due to changes in the normal regional differences in action potential duration. We assessed the contribution of potassium- and calcium-dependent currents to these differences. Both the altered sequence of ventricular repolarization and the underlying cellular mechanisms may contribute to the increased incidence of ventricular arrhythmias in hypertrophy. METHODS AND RESULTS: Rats received daily isoproterenol injections for 7 days. Myocytes were isolated from basal subendocardial (endo), basal midmyocardial (mid), and apical subepicardial (epi) regions of the left ventricular free wall. Action potentials were stimulated with patch pipettes at 37 degrees C. The ratio of heart weight to body weight and mean cell capacitance are increased by 22% and 18%, respectively, in hypertrophy compared with controls (P<.001). Normal regional differences in action potential duration at 25% repolarization (APD25) are reduced in hypertrophy (control: endo, 11.4+/-0.9 ms; mid, 8.2+/-0.9 ms; epi, 5.1+/-0.4 ms; hypertrophy: endo, 11.6+/-0.9 ms; mid, 10.4+/-0.8 ms; epi, 7.8+/-0.6 ms). The regional differences in APD25 are still present in 3 mmol/L 4-aminopyridine. Hypertrophy affects APD75 differently, depending on the region of origin of myocytes (ANOVA P<.05). APD75 is shortened in subendocardial myocytes but is prolonged in subepicardial myocytes (control: endo, 126+/-7 ms; epi, 96+/-10 ms; hypertrophy: endo, 91+/-6 ms; epi, 108+/-7 ms). These changes in APD75 are altered by intracellular calcium buffering. CONCLUSIONS: Normal regional differences in APD and the changes observed in hypertrophy are only partially explained by differences in I(tol). In hypertrophy, the normal endocardial/epicardial gradient in APD75 appears to be reversed. This may explain the T-wave inversion observed and will have implications for arrhythmogenesis.     

Angiography of left ventricle following volume load and physical work in coronary disease

In order to recognize and quantitate abnormalities in wall segment motion in 22 patients simultaneous measurements of isovolumic and ejection phase parameters were performed with the Millar-angiographic catheter at rest, after leg raising and during bicycle exercise. 6 patients had slight coronary heart disease (CHD) (group I), 16 patients had severe CHD (group II). During volume load in all patients of gr. II a decrease of peak measured velocity (Vpm) and the velocity of circumferential fiber shortening (Vcf from 1.4 to 1.1 circ/s, p less than 0.025) occurred. In gr. I Vcf increased (p less than 0.05). During exercise there was a high increase in Vpm and Vcf in gr. I (from 1.2 to 1.9 circ/s) whereas in gr. II no increase was observed. LVEDP rose to 29 mm Hg and ESV from 58 to 70 ml/1.73 m2. By increasing LVEDP during volume load underperfused areas became ischaemic and akinetic. During physical work the segmental abnormality can be less pronounced possibly due to the higher prestenotic pressure.     

Contribution of leukocyte infiltration to lipoperoxidation occurring in the non-ischemic region of the rat heart submitted to permanent left coronary artery occlusion

Previous studies have shown that during regional myocardial ischemia, the non-ischemic zone may be submitted to metabolic and structural alterations. In the present study, we have examined whether an inflammatory process could be responsible for increased lipoperoxidation in the non-ischemic zone of the rat heart subjected to permanent coronary artery ligation. Forty-eight hours after coronary artery ligation, tissue levels of malondialdehyde (MDA), taken as an index of lipoperoxidation, measured in the non-ischemic zone was increased by 25% when compared to sham operated hearts. Furthermore, an infiltration of polymorphonuclears was observed by immunofluorescence in the non-ischemic zone, while the activity of the neutrophil-specific myeloperoxidase enzyme (MPO) was significantly increased in that same zone (ligated 1.26 +/- 0.17 U/100 mg wet wt. v sham 0.33 +/- 0.01 U/100 mg wet wt.; P < 0.01). Examination of the temporal changes in MDA content and of MPO activity showed a significant linear decrease in both parameters of 6 to 48 h post-ligation. When compared to placebo, treatment with indomethacin (1 mg/kg, 5 min prior to ligation, then at 12 h intervals up to the harvesting of the hearts) led to a significant reduction in MDA content measured 6, 24 or 48 h after ligation. The treatment had no effect on infarct size measured 48 h after ligation. These results suggest that in the rat heart, permanent regional ischemia is associated with the rapid development of an inflammatory process in the non-ischemic zone which could in part account for the accumulation of lipoperoxidation products in that region.     

Effects of age and exercise training on size and composition of the rat left main coronary artery

This study evaluated the effects of age and exercise training on the left main coronary artery (LMCA) in young (Y-5 months) and old (O-27.5 months) female Fischer 344 rats. Both age groups were divided into trained (T) and weight-matched sedentary (S) control groups. Training consisted of 10 weeks of treadmill running progressing to a maximum workload of 15% grade, 1 hr/day, 5 d/wk at speeds of 36 and 15 m/min for the Y and O rats, respectively. Aging resulted in a 40% increase in left ventricle (LV) weight which was proportional to the increased body weight of the old animals. Exercise training produced a mild (approximately 10%) but significant left ventricular hypertrophy (LVH) in both trained groups. Cross-sectional area of the LMCA lumen and wall, wall thickness, and areas of collagen (C), elastin (E), and collagen-to-elastin ratio (C/E) of the LMCA wall were determined morphometrically in all four groups. A method for pinpointing the coronary ostium for use as a reference point was also developed. LMCA lumen area almost doubled (p < .001) across the measured age difference, but was unaffected by training. With aging, the increase in LMCA wall area bordered on significance (p < .053), while wall thickness, C area, and the C/E ratio were unchanged. Our results indicate that there is a disproportionate increase in the cross-sectional area of the rat LMCA with respect to LV mass changes with aging. This finding presumably reflects adaptation of this vessel to elevated resistances further downstream in the coronary circulation so that tissue perfusion can be maintained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac syncope due to transient coronary artery occlusion: the role of percutaneous angioplasty

A case of cardiac syncope is presented, associated with single vessel coronary disease. The mechanism of the syncope would appear to be a ventricular arrhythmia with transmural myocardial ischaemia due to transient occlusion of the diseased coronary artery. The symptoms and electrocardiographic abnormalities were reproduced and subsequently abolished by percutaneous coronary angioplasty.     

Effects of reperfusion on arrhythmias and death after coronary artery occlusion in the rat: increased electrical stability independent of myocardial salvage

OBJECTIVES: This study sought to delineate salvage-dependent from salvage-independent coronary reperfusion in acute myocardial infarction and the effects on spontaneously occurring arrhythmias and arrhythmic death in rats. BACKGROUND: Reperfusion of the infarct-related artery might increase electrical stability independently of salvage of ischemic myocardium. METHODS: In 98 conscious rats the electrocardiogram was monitored by telemetry for 48 h after MI, and all episodes of ventricular tachycardia (VT) and ventricular fibrillation (VF) were analyzed. Reperfusion at 45 min (RP45) (n = 15), 90 min (RP90) (n = 18) and 180 min (RP180) (n = 30) min was compared with permanent coronary artery occlusion (CAO) (n = 35) with respect to the post-reperfusion periods. RESULTS: RP45, RP90 and RP180 reduced the incidence of VT by 93%, 98% and 88% and VF by 89%, 97% and 92%, respectively (all p < 0.01 vs. CAO). The all-cause mortality rate was reduced from 47% (CAO) to 8% (RP45, p < 0.05) and 0% (RP90, p < 0.01); after RP180 it was 17% (CAO 42%, p = 0.08). All reperfusion regimens reduced arrhythmic deaths: 47% to 8% (RP45, p < 0.05), 47% to 0% (RP90, p < 0.01) and 42% to 8% (RP180, p < 0.05). Infarct size was identical to that during CAO (49 +/- 10% [mean +/- SD]) and RP180 (49 +/- 10%), whereas preferentially epicardial salvage occurred at RP45 (36 +/- 8%, p < 0.001) and RP90 (38 < 10%, p < 0.001). CONCLUSIONS: Early and late reperfusion reduce the incidence and duration of VT and VF in conscious rats with acute MI. Thereby, arrhythmia-related mortality is improved through the prevention of fatal VF episodes. Thus, reperfusion increases the electrical stability of the heart independently of myocyte salvage, as proposed by the open artery hypothesis.     

Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion

In anesthetized dogs the circumflex and/or the anterior descending coronary artery were briefly occluded (10 to 90 seconds) and ectopic beats occurring during the occlusion or for 60 seconds following release were counted. Control occlusions were alternated with occlusions performed during complete, reversible, unilateral blockade of either the right or the left stellate ganglion. This was achieved with thermodes through which coolant was circulated. In this way the shortcomings associated with stellectomy, which is irreversible, are avoided. Blockade of the right stellate ganglion increased the number of ectopic beats associated with coronary occlusion. The occurrence of episodes of ventricular tachycardia and fibrillation was also greater. By contrast, blockade of the left stellate ganglion reduced or abolished occlusion-induced arrhythmias. These effects are independent of changes in heart rate or vegal activity; they depend solely upon unilateral alteration in sympathetic tone, and are not demonstrable when such tone is low. We suggest that the right and left cardiac sympathetic nerves have a different influence upon cardiac excitability.     

The "bad" left ventricle. Results of coronary surgery and effect on late survival

Between 1968 and 1971, 252 patients with severe ventricular malfunction underwent revascularization surgery. By means of single-plane ventriculography, the ventricle was divided into six segments, three anteriorly and three inferiorly, and ejection fractions were calculated. Patients were classified into four groups according to these observations. Results were assessed in regard to relief of angina, graft patency status, surgical mortality rate, and survival as determined by actuarial life-table analysis. These results were then compared to over-all medical and surgical experience contained in the Milwaukee Cardiovascular Data Registry as well as to other reported series of medical treatment for similar degrees of coronary artery disease and impairment of left ventricular function. Comparison between the surgical and medical series suggests improved survival and improved quality of life in the surgically treated patients. Thus many patients with severe ventricular malfunction, especially if associated with angina, can be reasonably considered candidates for surgery.     

Effects of N-nitro-L-arginine on coronary artery tone and reactive hyperemia after brief coronary occlusion in conscious dogs

AIM: To determine the role of an endothelium-derived relaxing factor (nitric oxide) in controlling basal coronary tone and coronary vasomotion after brief coronary occlusion (reactive hyperemia). METHODS: In 10 chronically instrumented conscious dogs, we studied the diameter changes of the large epicardial coronary artery and coronary blood flow in response to intracoronary administration of acetylcholine (0.1 and 1 microgram) and brief coronary occlusion for 5 and 20 s before and after intracoronary infusion of N-nitro-L-arginine (LNNA). RESULTS: Intracoronary infusion of LNNA (1, 3, and 10 mg) decreased the diameter of the large epicardial coronary artery and coronary blood flow in a dose-dependent manner without altering arterial pressure and heart rate. LNNA (10 mg) significantly attenuated the increase in artery diameter and coronary blood flow by acetylcholine. The ratio of artery dilation to the blood flow response after acetylcholine was not affected by LNNA. LNNA (10 mg) significantly decreased the ratio of repayment to debt flow volume of reactive hyperemia, but did not affect the ratio of peak to resting flow; it also significantly attenuated the reactive dilation of the large epicardial coronary artery after reactive hyperemia. The ratio of artery dilation to repayment flow volume (micron/ml) during reactive hyperemia was attenuated significantly by LNNA. CONCLUSION: These findings suggest that endothelium-derived nitric oxide may contribute to basal coronary tone and that reactive dilation of the large epicardial coronary artery during reactive hyperemia was caused by flow-mediated nitric oxide release, whereas coronary artery dilation after acetylcholine was caused largely by the direct receptor-mediated release of nitric oxide.     

Estimates of regional work in the canine left ventricle

Assessment of the magnitude of regional myocardial work requires knowledge of regional fiber stress and fiber shortening. The theoretical development and experimental validation of a method is presented which used values of estimated active and passive fiber stress according to a fluid-fiber model, and measured fiber strain values. This enables the construction of regional stress-strain diagrams, a regional analog of the pressure-volume area model by Suga and co-investigators, which can be linked to regional oxygen consumption. In the left ventricle, either normally or asynchronously activated, the method yields reliable data on strain and active and passive fiber stress. The relation between estimated regional work and myocardial oxygen demand is in quantitative agreement with previously reported relations between global oxygen demand and measured pressure-volume area. During coronary artery occlusion, however, these values were less reliable, which might be due to inaqdequate knowledge of the (passive) material properties of the myocardium.