Selective suction and pressure-regulated retroinfusion: an effective and safe approach to retrograde protection against myocardial ischemia in patients undergoing normal and high risk percutaneous transluminal coronary angioplasty

OBJECTIVES: We sought to study the safety, feasibility and efficacy of selective suction and pressure-regulated retroinfusion to protect against myocardial ischemia in patients undergoing normal risk and high risk balloon angioplasty. BACKGROUND: In a pig model of acute myocardial ischemia it was previously shown that use of selective suction and pressure-regulated retroinfusion was able to substantially preserve regional myocardial function during ischemia with a higher efficacy than that obtained with unselective synchronized retroperfusion. METHODS: In 42 patients with normal risk (n = 27) or high risk (n = 15) percutaneous transluminal coronary angioplasty (PTCA), alternate balloon inflations of the left anterior descending coronary artery (60 s) were either supported or not supported by selective suction and pressure-regulated retroinfusion of the anterior interventricular vein. In an additional group of 10 patients with normal risk, retroinfusion was directly compared with autoperfusion during 10 min of ischemia. RESULTS: Balloon inflations without retroinfusion resulted in a decrease of regional myocardial function in the ischemic zone to 13% of baseline. In contrast, regional myocardial function was preserved at 76% of baseline (p < 0.05) during balloon inflation supported by retroinfusion. This preservation of regional myocardial function by retroinfusion was maintained during 10 min of ischemia with at least similar efficacy compared with autoperfusion. With retroinfusion, hemodynamic variables were stabilized in normal risk and high risk patients. No complications related to the catheterization of the anterior interventricular vein using a femoral approach (95% success rate) were observed, and clinical follow-up after 3 to 6 months was uneventful with regard to the coronary intervention. CONCLUSIONS: Use of selective suction and pressure-regulated retroinfusion was feasible and safe and had a high efficacy for preserving regional myocardial function and hemodynamic variables during PTCA in normal risk and selected high risk patients.     

Combining percutaneous bypass with coronary retroperfusion limits myocardial necrosis

After an acute coronary occlusion that results in hemodynamic instability, the institution of percutaneous bypass (PB) can effectively support the failing myocardium. However, PB cannot augment coronary blood flow, and substantial regional myocardial necrosis can still occur. This experimental study was undertaken to determine whether combining PB with coronary venous retroperfusion using pressure-controlled intermittent coronary sinus occlusion (PICSO) would limit myocardial necrosis after an acute coronary occlusion. In 30 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion with the snares released. During the period of coronary occlusion, 10 pigs were placed on PB, 10 pigs received PB+PICSO, and 10 pigs received no support (unmodified). Hearts treated with the combination of PB+PICSO had the highest wall motion scores (unmodified, 1.4 +/- 0.3; PB, 1.4 +/- 0.3; PB+PICSO, 2.8 +/- 0.3 [p < 0.05 versus unmodified and PB]) and the lowest area of necrosis in the area at risk (unmodified, 73% +/- 3%; PB, 43% +/- 2%; PB+PICSO, 14% +/- 2% [p < 0.05, PB and PB+PICSO versus unmodified; p < 0.05, PB+PICSO versus PB]). We conclude that combining PB with coronary venous retroperfusion significantly limits myocardial necrosis.     

Retrograde perfusion as a method for myocardial revascularization

Retroperfusion of the superficial coronary venous system was studied in 44 canine fibrillating in vivo, normothermic preparations, with exclusion of the systemic circulation using cardiopulmonary bypass techniques in order to assess its value as a method of myocardial revascularization. Perfusion of either the isolated aortic arch via a brachiocephalic cannula or of the coronary sinus through the free end of a vein anastomosed to the atrial rim of the sinus was performed for 1 h at 100 cm3/min in groups II-IV following 30 min of anoxia. Oxygen uptake, vascular resistance, venous outflow and venous enzyme levels (CPK, GDH) were studied. Group I controls (antegrade perfusion, no anoxia) showed continued aerobic metabolism in contrast to group II (antegrade perfusion) and III (retrograde perfusion) which displayed negative lactate balance. Oxygen consumption was greater in group III than II (p less than 0.01) with a higher oxygen extraction in III (p less than 0.005). Group IV, which was given intravenously 30 mg/kg methylprednisolone prior to anoxia and then retroperfused, showed continued aerobic metabolism with low GDH venous levels and adequate oxygen consumption. Three dogs were then subjected to aortoatrial rim coronary sinus vein grafts with ligation of the left common coronary artery at its bifurcation with distal left circumflex and anterior descending artery-internal mammary vein anastomoses for venous drainage. The right coronary artery was left intact. Arterial inflow into the coronary sinus was associated with a left ventricular pressure of 70-80 mm Hg for up to 1.5 h while regular sinus rhythm was maintained. We conclude that retroperfusion of the coronary sinus represents a surgically feasible technique for providing oxygen delivery to the ischemic myocardium.     

Usefulness of isometric hand grip exercise in detecting coronary artery disease during dobutamine atropine stress echocardiography in patients with either stable angina pectoris or another type of positive stress test

Dobutamine atropine stress echocardiography (DASE) detects coronary artery disease (CAD) by increasing myocardial oxygen demand causing ischemia. The sensitivity of the test for detection of CAD is reduced in patients with submaximal stress. We hypothesized that increasing cardiac work load by adding isometric exercise would improve the detection of ischemia during DASE. We studied 31 patients, mean age 57+/-11 years, with angiographically documented CAD. Patients underwent DASE using incremental dobutamine doses from 5 to 40 microg/kg/min, followed by atropine if peak heart rate was <85% of predicted maximal. Hand grip was then performed for 2 minutes at 33% of maximal voluntary contraction, while dobutamine infusion was maintained at the peak dose. The addition of hand grip during dobutamine stress was associated with a significant increase in systolic blood pressure (143+/-21 vs 164+/-24 mm Hg, p = 0.001) and left ventricular end-systolic circumferential wall stress (72+/-30 x 10(3) dynes/cm2 vs 132+/-34 x 10(3) dynes/cm2, p = 0.004). Wall motion score index increased from 1.0 at rest to 1.15+/-0.18 with dobutamine (p = 0.0004 vs rest), and increased further to 1.29+/-0.22 with the addition of hand grip (p = 0.004 vs dobutamine). Ischemia was detected in 19 patients (62%) with dobutamine-atropine stress alone and in 25 (83%) after the addition of hand grip (p <0.05). The addition of hand grip during DASE is feasible, and improves the detection of myocardial ischemia.     

Alterations of the architecture of subendocardial arterioles in patients with hypertrophic cardiomyopathy and impaired coronary vasodilator reserve: a possible cause for myocardial ischemia

OBJECTIVES: The study was designed to investigate the architecture of subendocardial arterioles of patients with hypertrophic cardiomyopathy (HCM) and angina pectoris with respect to coronary vasodilator reserve. BACKGROUND: There is growing evidence that the coronary microvasculature is abnormal in HCM. Arterioles, which mainly regulate intramyocardial blood flow, are especially suspect. METHODS: Thirteen patients with HCM (50.1+/-12.6 years old, mean value +/- SD) were studied after exclusion of any relevant coronary stenoses. Subendocardial arterioles (density [n/mm2], wall area [microm2], percent lumen area [%lumen], periarteriolar collagen area [microm2]), myocyte diameter (microm) and interstitial collagen fraction (Vv%) were evaluated by means of stereologic morphometry of transvenous biopsy samples. Coronary blood flow was measured quantitatively with the inert chromatographic argon method at basal conditions and after dipyridamole (0.5 mg/kg body weight over 4 min intravenously), and coronary vasodilator reserve was calculated as the ratio of coronary resistance at basal conditions and after pharmacologic vasodilation. Data from five normotensive subjects (45.4+/-11 years old, p = NS) served as control data. RESULTS: Arteriolar density was diminished by 38% (p = 0.004) and %lumen by 13% (p = 0.009) in patients with HCM compared with control subjects. Coronary reserve was impaired in patients with HCM (2.28+/-0.6 vs. 5.34+/-1.49, p = 0.003) because of higher coronary resistance after vasodilation (0.48+/-0.14 vs. 0.22+/-0.06 mm Hg x min x 100 g/ml, p = 0.004). Coronary vasodilator reserve correlated with arteriolar density (r = +0.47, p = 0.045) and with %lumen (r = 0.65, p = 0.003). CONCLUSIONS: In HCM, the architecture of preterminal subendocardial arterioles is altered by a reduced total cross-sectional lumen area, corresponding to an impaired coronary vasodilator capacity that may predispose to myocardial ischemia.     

Experimental application of synchronized coronary sinus retroperfusion (SCSR) and left heart bypass (LHB) for severe cardiogenic shock

In order to evaluate the efficacies of concomitant use of left heart bypass (LHB) and synchronized coronary sinus retroperfusion (SCSR) for ischemic cardiogenic shock refractory to conventional mechanical circulatory assist such as intra-aortic balloon pumping (IABP), experimental comparison studies were made in swine. The acute myocardial infarction model was made by left anterior descending coronary artery (LAD) ligation method. LHB was performed by centrifugal pump (BioMedicus BP-80), supporting flows of half cardiac output. SCSR catheter was inserted into coronary sinus (CS) through external jugular vein. Then arterial blood was pumped from femoral artery to CS with flow of 60 to 70 ml/min which was synchronized to electrocardiogram (ECG). These animals were supported by only SCSR or LHB, and SCSR + LHB, comparing each cardiac performances, infarcted areas and coronary flow. Infarcted areas were evaluated by epicardial mapping ECG. Coronary blood flow and velocity were analyzed by electromagnetic flow meter and ultrasonic pulse doppler velocimeter respectively. In LHB group, coronary blood flow and velocity were increased because of elevation of mean aortic pressure. In addition, LVdp/dt, LVEDP were decreased, indicating left ventricular decompression. However, the infarcted area was slightly reduced. In contrast, it was remarkably reduced by SCSR, and cardiac function recovered gradually from cardiogenic shock. In SCSR + LHB group, the ischemic area was significantly reduced and their hearts completely recovered from cardiogenic shock, demonstrating the good supply and demand balance of myocardial oxygen. The systolic reverse LAD flow and velocity which was increased due to cardiogenic shock, was remarkably reduced. These results suggested this concomitant new application is suitable for recovering from cardiogenic shock due to AMI which is not able to apply antegrade coronary perfusion.     

Prognosis of "clandestine" myocardial ischemia, silent myocardial ischemia, and angina pectoris in medically treated patients

The aim of this study was to assess the prognosis of medically treated patients with "clandestine" myocardial ischemia (perfusion defect without angina and no ST depression > 1 mm during exercise test) compared to those with silent myocardial ischemia (ST-segment depression > 1 mm, without angina) and those with angina pectoris. One hundred twelve patients without previous myocardial infarction were included. All patients underwent a symptom-limited exercise test on a bicycle ergometer, myocardial perfusion technetium-99m-methoxy-isobutyl-isonitrile single-photon emission computed tomography (SPECT), and coronary angiography. They were classified into 3 groups (angina group, 34 patients; silent group, 20 patients; and the clandestine group, 58 patients). The mean follow-up was 3.6 years (range 6 months to 5.5 years). Patients with clandestine ischemia had a lower scintigraphic and angiographic score than patients with silent ischemia (25+/-8 vs 31+/-9 and 24+/-8 vs 29+/-7, p = 0.008, respectively), but the prognosis was similar. Only angina and severe reversible SPECT defects were predictive for cardiac events: death + myocardial infarction + revascularization. We conclude that in medically treated patients without previous myocardial infarction, angina and severe reversible SPECT defects are predictive for cardiac events only when the need for revascularization is included as a cardiac event.     

Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia

BACKGROUND: We initiated a phase 1 clinical study to determine the safety and bioactivity of direct myocardial gene transfer of vascular endothelial growth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia. METHODS AND RESULTS: VEGF gene transfer (GTx) was performed in 5 patients (all male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease). Naked plasmid DNA encoding VEGF (phVEGF165) was injected directly into the ischemic myocardium via a mini left anterior thoracotomy. Injections caused no changes in heart rate (pre-GTx=75+/-15/min versus post-GTx=80+/-16/min, P=NS), systolic BP (114+/-7 versus 118+/-7 mm Hg, P=NS), or diastolic BP (57+/-2 versus 59+/-2 mm Hg, P=NS). Ventricular arrhythmias were limited to single unifocal premature beats at the moment of injection. Serial ECGs showed no evidence of new myocardial infarction in any patient. Intraoperative blood loss was 0 to 50 cm3, and total chest tube drainage was 110 to 395 cm3. Postoperative cardiac output fell transiently but increased within 24 hours (preanesthesia=4.8+/-0.4 versus postanesthesia=4.1+/-0.3 versus 24 hours postoperative=6. 3+/-0.8, P=0.02). Time to extubation after closure was 18.4+/-1.4 minutes; average postoperative hospital stay was 3.8 days. All patients had significant reduction in angina (nitroglycerin [NTG] use=53.9+/-10.0/wk pre-GTx versus 9.8+/-6.9/wk post-GTx, P<0.03). Postoperative left ventricular ejection fraction (LVEF) was either unchanged (n=3) or improved (n=2, mean increase in LVEF=5%). Objective evidence of reduced ischemia was documented using dobutamine single photon emission computed tomography (SPECT)-sestamibi imaging in all patients. Coronary angiography showed improved Rentrop score in 5 of 5 patients. CONCLUSIONS: This initial experience with naked gene transfer as sole therapy for myocardial ischemia suggests that direct myocardial injection of naked plasmid DNA, via a minimally invasive chest wall incision, is safe and may lead to reduced symptoms and improved myocardial perfusion in selected patients with chronic myocardial ischemia.     

Aspirin, oral anticoagulants, and heart failure]

This study tests the hypothesis that myocardial blood flow and coronary microvascular dilator capacity vary as a function of time after orthotopic heart transplantation in humans. Positron emission tomography measurements of myocardial blood flow were obtained at rest and during adenosine in 24 patients between 1 and 86 months after heart transplantation. At the time of the study all patients were clinically well and had angiographically normal epicardial coronary artery vessels. Patients were divided into 3 groups based on time from transplant to positron emission tomography measurement of myocardial blood flow: group 1 to 12 months (n = 9); group 13 to 34 months (n = 8); and group > or = 37 months (n = 7). Basal myocardial blood flow in group 1 to 12 months (1.86+/-1.01 ml/min/g) exceeded (p <0.05) that of group 13 to 34 months (1.17+/-0.73) and group > or = 37 months (0.98+/-0.34). In group 13 to 34 months, basal myocardial blood flow and maximal dilator capacity (minimal coronary vascular resistance with adenosine 36+/-12 mm Hg/ml/min/g) were comparable to that of normal volunteers (1.01+/-0.20 and 37+/-, respectively). In group > or = 37 months, maximal flow response to adenosine was reduced (2.54+/-1.25 vs 3.16+/-0.52, respectively, p = 0.06). Maximal dilator capacity in group > or = 37 months (60+/-34) was impaired versus group 1 to 12 months (36+/-10) and group 13 to 34 months (36+/-12; both p <0.05) as well as normals (37+/-9, p <0.05). During the first year after cardiac transplantation basal myocardial blood flow is elevated out of proportion to external determinants of myocardial oxygen demand, but maximal dilator capacity of the coronary microcirculation is normal. Between 1 and 3 years both basal myocardial blood flow and microvascular function tend to normalize. After 3 years, although basal myocardial blood flow is normal, microvascular dilator capacity is impaired.     

Hepatic outflow study after piggyback liver transplantation

BACKGROUND: Hepatic vein outflow is discussed in liver transplantation after preservation of recipient retrohepatic vena cava. The aim of this study was to compare two methods of suparahepatic caval anastomosis. METHODS: From January 1993 to January 1995, 81 patients received 88 liver transplants because of liver cirrhosis (n = 70), acute liver failure (n = 7), elective retransplantation after hepatic artery thrombosis (n = 2), giant hemangioma (n = 1), and combined liver-small bowel transplantation (n = 1). Seven patients underwent urgent retransplantation, 12 had preoperative transjugular intrahepatic portocaval stent, and 11 had portal vein thrombosis. Five patients required extracorporeal venous shunt. A total of 82 liver transplantations had preservation of RHVC, and 70 patients received temporary end-to-side portacaval shunt. Suprahepatic caval anastomosis was carried out in 52 patients (group 1) between the graft suprahepatic vena cava and the ostia of recipient left and median hepatic veins. Thirty patients (group 2) had associated 3 cm vertical cavotomy with partial clamping of RHVC. In the fourth postoperative month 20 patients from each group had pressure and gradient measurement made among the hepatic veins, right atria, and the RHVC. RESULTS: Mean pressure gradient between hepatic veins and right atria was 0.75 +/- 0.49 mm Hg in group 1 and 2.06 +/- 0.85 mm Hg in group 2. Between the RHVC and the right atria it was 0.63 +/- 0.5 mm Hg in group 1 and 2.22 +/- 1.29 mm Hg in group 2. A pressure gradient higher than 3 mm Hg was considered hemodynamically significant. This pressure gradient was found between the hepatic veins and right atria in 10% of patients in group 1 and 40% of patients in group 2 (p = 0.03) and between the RHVC and right atria in 15% of patients in group 1 and 30% of patients in group 2 (p = 0.3). CONCLUSIONS: Preservation of the recipient RHVC with recipient caval anastomosis at the ostia of the median and left hepatic veins is a reliable technique without any hepatic venous outflow alteration. Associated cavotomy is not necessary.     

Coronary sinus retroperfusion combined with intraaortic balloon pumping to perfuse the acutely ischemic myocardium

This study was planned to show the effect of retroperfusion and intraaortic balloon pumping (IABP) on myocardial hemodynamic recovery. Twelve dogs entered this study. Half of them received IABP and coronary sinus retroperfusion (CSPR) combination (Group II) and the remaining received IABP alone (Group I). Left anterior descending artery was occluded for a period of three hours. 15 minutes after occlusion IABP and IABP + CSRP were initiated. The average cardiac output was 1.41 +/- 0.18 L/min in the group I and 1.72 +/- 0.24 L/min in the group II (p < 0.03) after 3 hours of occlusion. Mean arterial pressure was 82.1 +/- 4.8 mmHg in the group I and 89.7 +/- 2.6 mmHg in the group II (p < 0.03). On the basis of this study it was concluded that CSRP + IABP could be an alternative treatment to IABP alone during the acutely developing ischemia.     

Ischemic preconditioning enhances donor lung preservation in the rat

BACKGROUND: Ischemic preconditioning achieved by brief periods of ischemia and reperfusion before a prolonged period of ischemia can significantly reduce the extent of cardiac damage in many mammalian species and human beings. In this study we used a rat model of single lung transplantation to show that ischemic preconditioning also occurs in the lung. METHODS: Rats randomly selected for ischemic preconditioning had their left main bronchus and pulmonary artery occluded for 5 minutes, followed by 10 minutes of reperfusion and ventilation. Lungs of control rats were ventilated for 15 minutes. The lungs were perfused with University of Wisconsin solution, then heart and lungs were excised en bloc and stored in University of Wisconsin solution at 0 degree C for 6 or 12 hours. After left pneumonectomy, the left lung of the donor was then implanted into the recipient via left thoracotomy. After 1 hour of ventilation and reperfusion, a right pneumonectomy was performed making the animal completely dependent on the transplanted lung. Samples of arterial blood from the left ventricle were then taken for arterial oxygen tension and arterial carbon dioxide tension determination. Water contents of the donor lungs were measured before and after reperfusion. Thiobarbituric acid reactive substances were measured in the right donor lung after storage. RESULTS: Lungs transplanted after 12 hours of storage had profoundly impaired gas exchange (arterial oxygen tension = 34 +/- 5; arterial carbon dioxide tension = 69 +/- 7 mm Hg) compared with the normal levels in the 6-hour storage group (arterial oxygen tension = 308 +/- 22; arterial carbon dioxide tension = 17 +/- 1 mm Hg). Ischemic preconditioning significantly improved gas exchange in the 12-hour storage group (arterial oxygen tension = 83 +/- 11; arterial carbon dioxide tension = 40 +/- 4 mm Hg). Ischemic preconditioning also significantly decreased thiobarbituric acid reactive substances formation at both 6- and 12-hour storage. CONCLUSIONS: These results show that the phenomenon of ischemic preconditioning occurs in the lung and that it may reduce injury to the donor lung during prolonged cold ischemic storage.     

Effects of ergotamine on myocardial blood flow in migraineurs without evidence of atherosclerotic coronary artery disease

The effects of intravenous ergotamine (0.25 mg) on basal and hyperemic (dipyridamole) myocardial blood flow (MBF), measured with positron emission tomography and H2(15)O, were assessed in 15 migraineurs in a double-blind, randomized, placebo controlled, crossover study. Ergotamine produced a 27% reduction in hyperemic MBF (2.62 +/- 0.11 vs 3.72 +/- 1.05 ml x min(-1) x g(-1); p <0.05), a 31% reduction in the coronary vasodilator reserve (1.81 +/- 0.50 vs 2.71 +/- 1.15; p <0.01), and a 55% increase in minimal coronary resistance (42.2 +/- 15 vs 26.7 +/- 8 mm Hg x min x ml(-1) x g(-1); p <0.001), suggesting vasoconstriction of the coronary microcirculation.     

Effects of alpha-adrenergic blockade on regional myocardial function in canine ischemic myocardium during beta-adrenergic blockade

OBJECTIVE: The contribution of alpha-adrenergic receptor subtypes in mediation of coronary vasoconstriction during ischemia remains controversial. This study investigated the effects of alpha-adrenergic subtypes blockade on regional myocardial function in a canine ischemic model. DESIGN: Prospective, randomized, controlled trial. SETTING: Experimental animal laboratory in a university medical center. PARTICIPANTS: Thirty-two adult dogs, weighing 13 to 22 kg. INTERVENTIONS: The animals were prepared with pentobarbital, oxygen, enflurane and pancuronium. Two selective alpha 1-adrenergic antagonists (bunazosin, 50 micrograms/kg/min, n = 8, and prazosin, 25 micrograms/kg/min, n = 8) and the alpha 2-adrenergic antagonist (yohimbine, 15 micrograms/kg/min, n = 8) were administered after the partial occlusion of the left circumflex coronary artery (LCX) during beta-adrenergic blockade (propranolol, 1 mg/kg). MEASUREMENTS AND MAIN RESULTS: Myocardial systolic segment shortening (%SS) and a myocardial lactate extraction ratio (LER) were used as indices of regional myocardial and metabolic function. Compared with poststenotic condition, coronary blood flow of the LCX was increased by 123% with bunazosin and 138% with prazosin (p < 0.05, respectively). Both %SS and LER in the ischemic myocardium were significantly improved after treatment with both alpha 1-adrenergic antagonists (in the bunazosin group, %SS, 8.3 +/- 1.9 to 10.4 +/- 2.2%, p < 0.05; LER, -12.8 +/- 12.3 to 6.2 +/- 15.9%, p < 0.01; in the prazosin group, %SS, 8.5 +/- 1.6 to 10.3 +/- 1.9%, p < 0.05; LER, -10.2 +/- 5.7 to 3.6 +/- 10.2%, p < 0.05). In contrast, coronary blood flow of the LCX, %SS and LER were not different from poststenotic condition during alpha 2-adrenergic receptor blockade with yohimbine. The salutary effect of bunazosin was also observed after mechanically controlling for the afterload reduction produced by alpha 1-adrenergic blockade (n = 8). Prazosin and yohimbine were found to produce a significant increase in plasma norepinephrine levels in contrast to bunazosin, which had no significant effect. CONCLUSIONS: These data indicate that alpha 1-adrenergic blockade increases coronary blood flow and improves regional myocardial function during myocardial ischemia.     

Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning"

OBJECTIVES: This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect. BACKGROUND: Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemia and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC. METHODS: Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy. RESULTS: RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8+/-3.5%, 18.2+/-1.8%*, 19.6+/-1.3%*, 44.9+/-5.0%, 35.6+/-2.7% and 34.8+/-3.6% of the area at risk (*p < 0.05 vs. CNT), respectively. CONCLUSIONS: PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.     

Hemodynamic effects of the implantation of an intracaval oxygenator

Treatment of severe respiratory failure by extracorporeal membrane oxygenation (ECMO) is complex. However, there is now an intravascular gas exchanger (IVOX) available that provides extrapulmonary gas transfer without requiring an extracorporeal blood path. The present study was performed to determine the hemodynamic effects resulting from the intracaval placement of the intravascular device. A bovine model (n = 6; body-weight = 72 +/- 5 kg) was selected for temporary lung support with the intravascular device. The latter was placed in the caval axis under fluoroscopic control after full instrumentation of the animal for hemodynamic measurements including a pulmonary artery catheter for determination of cardiac output by thermodilution and continuous readout of mixed venous oxygen saturation. All measurements were taken after a stabilization period of 15 min. The heart rate moved from 65 +/- 8 before to 72 +/- 10 after implantation and 68 +/- 9 after onset of intravascular gas exchange (NS). Right atrial pressure was 13 +/- 3 mm Hg before, 12 +/- 3 mm Hg after implantation and 10 +/- 3 mm Hg after onset (NS) whereas femoral venous pressure moved from 14 +/- 3 mm Hg to 17 +/- 4 mm Hg (p < 0.05) and remained at 17 +/- 4 mm Hg after onset. Cardiac output was 5.3 +/- 0.7 l/min before, 5.4 +/- 0.7 l/min after implantation and 5.3 +/- 1.1 l/min after onset (NS) while mixed venous oxygen saturation dropped from 60 +/- 7% to 54 +/- 11% and moved to 57 +/- 11 after onset of the device (NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Resection of the metatarsal head for diabetic foot ulcers

Dobutamine-induced hypotension has been disregarded as a marker of more severe functional abnormalities in patients with suspected coronary artery disease. However, its functional significance in patients with myocardial infarction has not been studied. The aim of this study was to define the predictors of systolic blood pressure (SBP) response to dobutamine in patients with previous myocardial infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography was performed in 326 patients with prior myocardial infarction referred for evaluation of myocardial ischemia. A 16-segment, four-grade score model was used to assess left ventricular function. Wall motion score index was derived by summation of wall motion score divided by 16. SBP and heart rate increased from rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs 122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred in 50 patients (15%). By multivariate analysis, independent predictors of failure of SBP increase were higher peak wall motion score index (p < 0.001), higher resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05). SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of SBP drop were higher resting wall motion score index (p < 0.001), higher resting SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial infarction, left ventricular function and baseline systolic blood pressure are powerful predictors of SBP response to dobutamine stress testing.     

Vasodilation with adenosine or sodium nitroprusside after coronary artery bypass surgery: a comparative study on myocardial blood flow and metabolism

The effects of adenosine and sodium nitroprusside (SNP) on central hemodynamics and myocardial blood flow and metabolism were investigated postoperatively after elective coronary artery bypass (CABG) surgery in ten sedated and mechanically ventilated patients in the intensive care unit. During three consecutive 15-min periods, SNP (0.8 +/- 0.1 micrograms.kg-1 x min-1), adenosine (88.9 +/- 13.3 micrograms.kg-1 x min-1), and then again SNP (0.7 +/- 0.1 micrograms.kg-1 x min-1) were infused to control postoperative hypertension at a mean arterial pressure of approximately 80 mm Hg. Systemic and pulmonary hemodynamics and global (coronary sinus flow, CSF) as well as regional (great cardiac vein flow, GCVF) myocardial blood flow and metabolic variables were measured. During adenosine infusion, in comparison to SNP, heart rate was unchanged, stroke volume index and cardiac index increased (24% and 32%, respectively), and the systemic vascular resistance index decreased (-26%). Mean pulmonary arterial pressure (24%) as well as pulmonary capillary wedge pressure (27%) and central venous pressure (18%) were higher with adenosine compared to SNP. Adenosine also increased CSF and GCVF (108% and 103%, respectively) without altering the CSF/GCVF flow ratio compared to SNP. Furthermore, adenosine increased the coronary oxygen content (51%) and decreased the arterio-great cardiac vein oxygen content difference (-48%) without changing regional myocardial oxygen consumption, indicating a more pronounced hyperkinetic myocardial circulation compared to SNP. In addition, adenosine infusion decreased arterial PO2 (-11%) and increased the intrapulmonary shunt fraction (57%). The PR interval time of the electrocardiogram was prolonged (12%) and the ST segment was more depressed during adenosine infusion compared to SNP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measuring oxygen tension in the anterior chamber of rabbits

PURPOSE: Measuring the concentration of oxygen in the aqueous humor without penetrating the eye would provide a new dimension in understanding aqueous humor and corneal dynamics. In this study a preinvasive method was developed for determining the cameral oxygen concentration in anesthetized rabbits by measuring the excited-state lifetime of a phosphorescent dye. METHODS: A scanning ocular fluorometer was designed to excite phosphorescence with a brief flash of light and to measure the decay of luminescence for as long as 1000 microsec after excitation. The measurement window was scanned through the depth of the anterior chamber or fixed at the mid-anterior chamber. A depot of the phosphorescent dye Pd-uroporphyrin was injected into the vitreous of eight pigmented rabbits, and within a few days the dye was measurable in the anterior chamber. The excited-state lifetime of this dye is inversely correlated to oxygen concentration and was calibrated by measuring the lifetime of dye in cuvettes equilibrated with oxygen-nitrogen mixtures. Oxygen tensions were determined from lifetimes measured in the open eye, under a polymethylmethacrylate (PMMA) contact lens, under two oxygen-permeable contact lenses, and immediately after lid closure. RESULTS: Oxygen tension in the mid-anterior chamber before placing a PMMA contact lens was 23 +/- 3 mm Hg (mean +/- SD; n = 6). After 20 minutes of PMMA lens wear, oxygen tension decreased to 4 +/- 2 mm Hg. When the focal diamond was scanned through the anterior chamber, oxygen tension was 24 +/- 5 mm Hg near the corneal endothelium and decreased to 17 +/- 8 mm Hg near the crystalline lens. Under the PMMA contact lens this gradient reversed: Oxygen tensions near the endothelium and lens were 3 +/- 2 mm Hg and 6 +/- 2 mm Hg, respectively. Lid closure for 10 minutes or longer decreased the mid-anterior chamber oxygen tension from 21 +/- 2 mm Hg (n = 19 measurements from seven animals) to 10 +/- 3 mm Hg (n = 15 measurements from five animals). CONCLUSIONS: Measuring excited-state lifetime of phosphorescent dyes in the anterior chamber provides a useful method for determining oxygen concentration in vivo, without penetrating the eye. Cameral oxygen tension under PMMA contact lenses are significantly lower than in the uncovered eye. The profile of oxygen tension through the anterior chamber suggests that oxygen is supplied transcorneally to the aqueous humor.     

Serum levels of basic fibroblast growth factor in acute myocardial infarction

As it has been reported that basic fibroblast growth factor (bFGF) is a circulating peptide and bFGF gene expression is increased after myocardial ischemia, this study was designed to investigate the serum levels of bFGF in patients with acute myocardial infarction (AMI). Using a bFGF enzyme-linked immunoassay, bFGF levels were determined in venous blood of 15 patients with AMI on admission, at 10 days, and 30 days after infarction, and of 15 age-matched healthy volunteers who were used as controls. bFGF serum levels on admission were similar to normal values (7.48 +/- 2.3 vs 8.14 +/- 2.9 pg/ml). However, they significantly increased (16.82 +/- 3.4 pg/ml; p <0.05) 10 days after the onset of AMI, and at 30 days they returned to baseline (7.07 +/- 2.9 pg/ml). The increased bFGF levels at the second week post AMI suggest that bFGF plays an important role in mediating the development of coronary collateral circulation after myocardial ischemia in humans.