Acute Myocardial Ischemia Model Research Articles

Pathological assessment of stem cell therapy for myocardial ischemic disease

The aim of this work was to investigate major unresolved issues in cardiac stem cell therapy, including the optimal types and doses, the optimal delivery methods, and the biosafety and efficacy. In a canine acute myocardial ischemia model, we studied differences in bone marrow mesenchymal stem cell (BM-MSCs) distribution when delivered by transendocardial (TE) or intracoronary (IC) route. 10 Adult dogs (6 TE, 4 IC) received DAPI-labeled allogenic BM-MSCs (100×l06 cells) 7 days after occlusion/reperfusion of the left anterior descending (LAD) and were sacrificed 14 days later.

Antiischemic and antiarrhytmic effects of angiotensin-converting enzyme inhibitor zofenopril in the rat model of acute myocardial ischemia

Angiotensin-converting enzyme (ACE) inhibitors are widely used in heart failure therapy, but little is known about their antiischemic effccts. The primary aim of this study was to investigate antiischemic effectiveness of SH-containing ACE inhibitor zofenopril in rats in comparison to captopril. The results provide an evidence that zofenopril, in contrast to captopril, reduces infarct size when administered intravenously at a dose of 2,5 mg/kg 30 minutes before ischemia. Antiischemic effect of zofenopril may be due to its high affinity to myocardial tissue. Unlike captopril, zofenopril exerted significant antiarrhythmic effect against ischemic ventricular tachyarrhytmias. Antiischemic effect of zofenopril was evident at a relatively high dose only and, therefore, was associated with considerable hypotensive effect.

Effect of Levosimendan and Milrinone on Regional Myocardial Ischemia/Reperfusion-Induced Arrhythmias in Dogs

Phosphodiesterase inhibitors as inodilators in heart failure are associated with promotion of arrhythmias. Calcium sensitizers have been proposed for the treatment of severe decompensated heart failure. The effect of levosimendan, a calcium sensitizer, and milrinone, a phosphodiesterase inhibitor, on ventricular arrhythmias was compared in a model of acute regional myocardial ischemia and reperfusion. The left anterior descending coronary artery in dogs was occluded for 25 minutes, followed by reperfusion. The 2 drugs were administered in a hemodynamically equieffective dose (0.1 micromol/kg) 10 minutes before coronary occlusion. Levosimendan, but not milrinone, significantly attenuated the pronounced increase in the number of ventricular premature beats (-63%), tachycardia (-50%), fibrillation (-70%), and inhomogeneity of ventricular electrical activation. Levosimendan significantly improved the overall survival rate. Levosimendan has a more beneficial profile than milrinone regarding the development of ventricular arrhythmias during and after regional myocardial ischemia.

Effect of acupuncture at acupoint Neiguan (PC 6) on the myocardial c-fos gene expression of acute myocardial ischemia in rats

Objective: To investigate the mechanism of improvement effect of electro-acupuncture at acupoint Neiguan (PC 6) on acute myocardial ischemia (AMI).Methods: Ninety-six rats were randomly divided into sham-operation group, myocardial ischemia model group and myocardial ischemia model plus electro-acupuncture group, the rat model of AMI was established by occlusion of the anterior descending branch of the left coronary artery, then electro-acupuncture therapy was performed at bilateral acupoint Neiguan (PC 6). The myocardial enzyme activities in plasma was detected with biochemical method, and the myocardial c-fos gene expression was detected with reverse transcription polymerase chain reaction (RT-PCR) method.Results: The myocardial enzyme activities in plasma and the myocardial c-fos gene expression in myocardial ischemia model group were obviously higher than those in sham group(P<0.05), after electro-acupuncture treatment, the myocardial enzyme activities in plasma and the myocardial c-fos gene expression were decreased, there was a significant difference (P<0.05).Conclusion: The mechanism of improvement effect of electro-acupuncture at acupoint Neiguan (PC 6) on AMI is related to down-regulation of the myocardial c-fos mRNA expression.

Whole Blood Cardioplegia (Minicardioplegia) Reduces Myocardial Edema After Ischemic Injury and Cardiopulmonary Bypass

While blood:crystalloid cardioplegia is the clinical standard for patients undergoing cardiopulmonary bypass (CPB), it has been postulated that whole blood minicardioplegia may benefit the severely injured heart by reducing cardioplegic volume, thereby reducing myocardial edema. To test this hypothesis, we compared the cardioprotection of a popular 4:1 blood:crystalloid cardioplegia to whole blood minicardioplegia (WB) in a porcine model of acute myocardial ischemia. Yorkshire pigs (n = 20) were placed on atriofemoral bypass and subjected to 30 minutes of global normothermic ischemia. Animals were randomized to receive either 4:1 cold cardioplegia (n = 10) or WB cold cardioplegia (n = 10) delivered antegrade continuously for 90 minutes. Baseline (BL) echocardiographic determination of left ventricular mass (LVM) was compared within groups for cardiac edema (%) measured by histologic morphometrics. All (100%) animals receiving WB were successfully weaned off CPB, whereas only 40% of animals receiving 4:1 were successfully weaned off CPB. Cardiac edema percentage (p &lt; .004) and LVM (p &lt; .05) were significantly decreased in the WB group compared with 4:1. WB cardioplegia increases the number of hearts successfully weaned from CPB and decreases cardiac edema in our porcine model of acute myocardial ischemia. This finding implies whole blood cardioplegia may be more protective in a select group of patients undergoing extended CPB time by decreasing myocardial edema.

Mildronate, a Novel Fatty Acid Oxidation Inhibitor and Antianginal Agent, Reduces Myocardial Infarct Size Without Affecting Hemodynamics

Mildronate is a fatty acid oxidation inhibitor approved as an antianginal drug in parts of Europe. We carried out the first study to determine whether a 10-day course of mildronate could reduce myocardial infarct size (IS) during acute myocardial ischemia. Sprague Dawley rats received 200 mg/kg/d of mildronate (treated group, n = 16) or sterile water (control group, n = 14) subcutaneously for 10 days before ischemia-reperfusion. Rats were then subjected to 45 minutes of left coronary artery occlusion and 2 hours of reperfusion. The 2 groups had identical areas at risk: treated 38 +/- 3%; controls 38 +/- 2%. The amount of necrosis was smaller in the mildronate group at 16 +/- 2% of the left ventricle versus controls, 22 +/- 2% (P = 0.05); and for any amount of risk >25%, necrosis was smaller in the treated group (P = 0.0035). Myocardial IS (% of risk zone) was 43+/-3% in the mildronate-treated rats, and 57+/-4% in controls (P = 0.004). During occlusion, there were no differences between the 2 groups in heart rate (216 +/- 12 bpm, mildronate and 210 +/- 9 bpm, control), in mean arterial pressure (60 +/- 2 mm Hg, mildronate and 64 +/- 3 mm Hg, control) or in the frequency of arrhythmias. Our study for the first time demonstrated that a 10-day treatment with mildronate reduced myocardial IS in an experimental model of acute myocardial ischemia, without any effect on hemodynamics.

Contrast Echocardiography: A Valid and Sensitive Imaging Method in the Investigation of Transmyocardial Laser-Revascularization in an Acute Ischemia Model

In an acute porcine myocardial ischemia model we examined the effect of transmyocardial laser-revascularization (TMLR) on the regional micro perfusion and oxygen supply. In clinical practice, contrast echocardiography is a reliable tool for the measurement of changes in regional blood flow in the ischemic myocardium. We compared contrast echocardiography with the laser Doppler measurement of micro perfusion and with the quantification of regional tissue oxygen tension using a Clark electrode. 22 pigs were randomised in the interventional group and 12 in the control group. Measurements with all three methods were performed before and after occlusion of the first diagonal branch of the left anterior descending coronary artery and, in the interventional group, after TMLR. We investigated not only the effects in the dependent ischemic myocardium, but also in two other myocardial areas, not involved in the coronary occlusion. There was a significant effect of TMLR on regional micro perfusion and local oxygen tension in the dependent ischemic myocardial area. Contrast echocardiography is a successful experimental tool to measure changes in regional myocardial perfusion which cannot be perceived using clinical imaging methods.

Quantification of resting myocardial blood flow in a pig model of acute ischemia based on first‐pass MRI

Qualitative and semiquantitative contrast-enhanced (CE) dynamic perfusion MRI techniques are established as noninvasive diagnostic means of assessing coronary artery disease. However, to date quantification of myocardial blood flow (MBF) has not reached the same acceptance as MBF quantification with nuclear techniques. To validate quantification of MBF at rest using the extracellular contrast agent (CA) Gd-DTPA, we performed an animal study in a pig model of acute myocardial ischemia. We quantified MBF from MRI data with a mathematical model (MMID4) of the underlying vasculature. These MBF results were subsequently compared with the results from fluorescent microspheres. The study showed a correlation of r = 0.66 between MBF estimates obtained with MRI and those obtained with fluorescent microspheres. The correlation for ischemic and nonischemic myocardium was r = 0.86 and r = 0.47, respectively. In conclusion, quantification of resting MBF using MMID4 is a valid method under conditions of acute myocardial ischemia.

Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat.

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), ventricular tachycardia (VT), or cardiac ischemia that show a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common antiarrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats (n = 49) were anesthetized with pentobarbital sodium (60 mg.ml(-1).kg(-1) i.p.) and instrumented for regional coronary occlusion (30 min) and reperfusion (120 min). Heart rate, blood pressure, and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 min before ischemia and extended throughout ischemia, terminating at the start of reperfusion. After 120 min, hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls (n = 12), 50% of adenosine only (305 microg.kg(-1).min(-1), n = 8), 0% in lidocaine only (608 microg.kg(-1).min(-1), n = 8), and 0% in AL at any dose (152, 305, or 407 microg.kg(-1).min(-1) adenosine plus 608 microg.kg(-1).min(-1) lidocaine, n = 7, 8, and 6). VT occurred in 100% of saline controls (18 +/- 9 episodes), 50% of adenosine-only (11 +/- 7 episodes), 83% of lidocaine-only (23 +/- 11 episodes), 60% of low-dose AL (2 +/- 1 episodes, P < 0.05), 57% of mid-dose AL (2 +/- 1 episodes, P < 0.05), and 67% of high-dose AL rats (6 +/- 3 episodes). VF occurred in 75% of saline controls (4 +/- 3 episodes), 100% of adenosine-only-treated rats (3 +/- 2 episodes), and 33% lidocaine-only-treated rats (2 +/- 1 episodes) of the rats tested. There was no deaths and no VF in the low- and mid-dose AL-treated rats during ischemia, and only one high-dose AL-treated rat experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats but only reached significance with the mid-dose treatment (saline controls 61 +/- 5% vs. 38 +/- 6%, P < 0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window in ischemic and nonischemic regions of the heart.

Insulin Attenuates the Systemic Inflammatory Response in a Rat Model of Acute Myocardial Ischemia and Reperfusion

Insulin Attenuates the Systemic Inflammatory Response in a Rat Model of Acute Myocardial Ischemia and Reperfusion

Primary study of vascular endothelial growth factor immunohistochemical staining in the diagnosis of early acute myocardial ischemia

The expression of vascular endothelial growth factor (VEGF) in the model of rat early acute myocardial ischemia was studied by Strept–Avidin–Biotin–Peroxidase Complex (SABC) immunohistochemical staining. After ligating the anterior descending branch of the left coronary artery, an initial rapid (30min) positive expression of VEGF in myocardial ischemic areas was observed, the intensity of positive expression of VEGF increased with the continuation of myocardial ischemia. After 5h infarction, the strongly positive myocytes of SABC-VEGF staining were predominantly limited to perimyocardial infarction areas. No positive expression of VEGF was found in the control group. These findings suggested that SABC-VEGF method could give a sensitive, specific, simple and objective morphologic evidence to the diagnosis of sudden cardiac death caused by acute early myocardial ischemia.

Effects of acute and chronic angiotensin receptor blockade on myocardial vascular blood volume and perfusion in a pig model of coronary microembolization

Based on the reduction of ischemic cardiac events in clinical trials and experimental observations, inhibition of the effects of angiotensin II on coronary microcirculatory function may afford myocardial protection after injury. The immediate effects of intracoronary AT 1 receptor blockade with irbesartan were examined in a pig model in the healthy myocardium and in acute ischemia induced by injection of 30-μm microspheres into the left anterior descending coronary artery (LAD). Electron-beam computed tomography was performed for in-vivo quantitative measurements of regional intramyocardial vascular blood volume (V B ) and perfusion (F M ), as well as left ventricular ejection fraction (LVEF) and muscle mass. Ratios of V B and F M in the anterior (LAD-supplied)/inferior (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected into the LAD increased V B and F M ratios significantly by 27 ± 8% and 51 ± 13%, respectively. After anterior coronary microembolization, V B and F M ratios were 0.60 ± 0.05 and 0.51 ± 0.05, respectively, and were significantly increased by irbesartan (by 24 ± 10% and by 36 ± 11%, respectively). After 4 weeks of treatment with oral irbesartan (n = 7) or placebo (n = 7), an improved LVEF (56 ± 4% v 44 ± 4%, P = .046) was observed in irbesartan-treated animals, but no difference in LV end-diastolic volumes or muscle mass. Resting V B (0.95 ± 0.06 v 0.76 ± 0.06; P = .047) and F M (0.84 ± 0.05 v 0.64 ± 0.04; P = .016) ratios were significantly greater in irbesartan-treated animals. Using adenosine, there was a trend for higher V B and F M ratios in irbesartan- v placebo-treated animals. Therefore, in a pig model of acute myocardial ischemia, AT 1 receptor blockade by irbesartan induced microvascular vasodilation and, ostensibly, conveyed myocardial protection. Long-term treatment with irbesartan resulted in moderate enhancements of resting V B and F M compared with placebo, suggesting a role for coronary microcirculatory effects of chronic AT 1 receptor blockade in preserving LVEF.

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.

The determination of myocardial viability using Gd-DTPA in a canine model of acute myocardial ischemia and reperfusion.

The partition coefficient of Gd-DTPA was thought to vary with the amount of cellular membrane damage after an acute myocardial infarction. The relationship between the partition coefficient of Gd-DTPA (lambda) and the uptake of 201Tl (as a marker of tissue viability) was studied 2 h to 3 weeks after reperfusion of a 2-h occlusion to the left anterior descending coronary artery in a canine model. Gd-DTPA was infused as a bolus followed by a prolonged constant infusion, and this infusion protocol was optimized such that the concentration of Gd-DTPA was directly related to lambda. After this infusion, MR images of excised hearts showed regions of increased signal intensity corresponding to increased Gd-DTPA concentration. At all time points, lambda and 201Tl uptake were strongly negatively correlated indicating that lambda is an accurate indicator of myocardial viability. Furthermore, lambda in the infarcted regions was increased relative to normal regions after 2 h of reperfusion and stayed elevated up to 3 weeks. At all time points, lambda in the infarcted and normal regions were significantly different. As well, this data showed a trend that lambda in infarcted regions decreased monotonically from 1 day to 3 weeks. This trend was confirmed with MR imaging by examining the change in signal intensity of in vivo images from 4 days to 3 weeks in two animals. These results suggest that MRI with Gd-DTPA could be used to measure the extent of myocardial damage after an acute myocardial infarction.

Effects of compound salviae miltiorrhizae injection on metabolism of phosphoinosititides in myocardial ischemia

Using the model of acute myocardial ischemia in rats formed by ligation of the descending anterior branch of the left coronary artery, this study showed some effects of compound Salviae miltiorrhizae injection (CSMI) on metabolism of phosphoinositide in myocardial ischemia. The results of the experiment showed that after 10 minutes of acute ischemia, the function of myocardial messangers of phosphoinositide increased, and the levels of phosphatidylinositol-4, 5-biphosphate (PIP2) and inositol-1, 4, 5-trisphosphate (IP3) were obviously higher than those of the non-ischemia control groups (P<0.01, n=7). CSMI (2 g/kg body weight) could markedly inhibit myocardial PIP2 and IP3, whose levels became lower than those of the ischemia control groups (P<0.01, n=7).

Load independence of radionuclide diastolic filling measurements in acute coronary occlusion

An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease. The time constant of isovolumic relaxation (T) and the left atrioventricular gradient were measured with micromanometer catheters and diastolic left ventricular filling variables were measured with radionuclide ventriculography in nine anesthetized, open-chest dogs with an acute coronary artery occlusion. Infusion of the positive inotropic drug dobutamine hydrochloride (5 to 10 micrograms/kg/min) resulted in a 35% shortening of T and a 37% increase in the radionuclide first-half filling fraction (both p < 0.05), but no change in the left atrioventricular gradient. Conversely, infusion of the alpha-adrenergic vasoconstrictor phenylephrine hydrochloride (20 to 40 micrograms/min) augmented left ventricular load, increasing the atrioventricular gradient by 45%, but had no significant effect on T or the first-half filling fraction. Infusion of the direct-acting vasodilator, sodium nitroprusside (80 to 120 micrograms/min), was accompanied by a 14% lengthening of T with a corresponding 28% decrease in the first-half filling fraction (both p < 0.05). In an anesthetized, open-chest canine model of acute myocardial ischemia, the radionuclide first-half filling fraction reflects pharmacologically induced changes in the lusitropic state of the left ventricle with relative independence of loading conditions.

A chimeric IgG4 monoclonal antibody directed against CD18 reduces infarct size in a primate model of myocardial ischemia and reperfusion

This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion. Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarct-related artery patency in patients with acute myocardial infarction. Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [+/- SD] 11 +/- 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay. Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 +/- 20% in the saline-treated group to 19 +/- 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons. Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.

Revascularization for acute regional infarct: Superior protection with warm blood cardioplegia

Continuous retrograde warm blood cardioplegia was compared with two widely used hypothermic myocardial protection techniques in a canine model of acute regional myocardial ischemia with subsequent revascularization. Animals (n = 30) underwent 45 minutes of left anterior descending coronary artery occlusion then cardioplegic arrest (60 minutes), followed by separation from caidiopulmonary bypass and data collection. The cold oxygenated crystalloid cardioplegia group (CC; n = 8) and the cold blood cardioplegia group (CB; n = 10) had cardiopulmonary bypass at 28 °C, antegrade arrest, and intermittent retrograde delivery. The warm blood cardioplegia group (WB; n = 12) had normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery. Overall ventricular function (preload recruitable stroke work relationship; ergs × 10 3/mL) was significantly ( p < 0.001) better for WB (WB, 80 ± 11; CB, 67 ± 13; CC, 57 ± 12). Systolic function (maximum elastance relationship; mm Hg/mL) was also significantly ( p < 0. 001) better for WB (WB, 11.6 ± 3.6; CB, 8.6 ± 2.7; CC, 6.2 ± 1.3). Diastolic function (stress-strain relationship; dynes × 10 3/cm 2) revealed significantly ( p < 0.001) decreased compliance for CC (WB, 20 ± 6; CB, 19 ± 7; CC, 27 ± 11). Left anterior descending coronary artery regional adenosine triphosphate/adenosine diphosphate ratios were significantly ( p = 0.02) worse for CC (WB, 10.2 ± 2.3; CB, 9.4 ± 2.6; CC, 5.6 ± 1.5). Myocardial edema significantly ( p =0.03) increased over time only in the CC animals (WB, 0.4% ± 2.3%; CB, −0. 3% ± 3.6%; CC, 5.5% ± 2.3%). In this model of acute regional myocardial ischemia and revascularization, continuous retrograde warm aerobic blood cardioplegia provided superior myocardial protection compared with cold oxygenated crystalloid cardioplegia with intermediate results for cold blood cardioplegia.

Warm blood cardioplegia: Superior protection after acute myocardial ischemia

Three myocardial protection techniques were studied in a canine model of acute myocardial ischemia with subsequent revascularization. Eighteen animals were randomly assigned to one of three treatment regimens: cold oxygenated crystalloid cardioplegia (CC), cold blood cardioplegia with modified reperfusate (CB), and continuous aerobic warm blood cardioplegia (WB) (n = 6 per group). Systemic hypothermic cardiopulmonary bypass (28 °C), antegrade arrest, and intermittent retrograde and antegrade delivery were used for the CC and CB groups. Systemic normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery were used for the WB group. Fifteen minutes of warm global ischemia was followed by occlusion of the left anterior descending coronary artery (15-minute duration) and simultaneous initiation of cardioplegic arrest (60-minute duration) to simulate clinical revascularization. After reperfusion, the animals were separated from cardiopulmonary bypass. Myocardial function, electrocardiogram, myocardial energetics, water content, histopathology, and defibrillation requirements were compared between groups. There was no significant difference in maximum elastance, myocardial oxygen consumption, myocardial edema, or histopathologic evidence of injury between groups. However, overall ventricular function, assessed by the slope of the preload recruitable stroke work relationship, was significantly better for the WB group ( p = 0.04) (WB, 73 ± 9; CB, 56 ± 7; CC, 47 ± 5). Diastolic function as assessed by the slope of the stress-strain relationship was significantly worse overall for the cold groups ( p = 0.001) (WB, 20 ± 2.2; CB, 39 ± 1.3; CC, 37 ±3.1). Myocardial injury as assessed by ST segment elevation (millimeters) was less for the WB group ( p = 0.03) (WB, 0.4 ± 0.3; CB, 1.7 ± 0.2; CC, 1.6 ± 0.7). Countershocks necessary to restore sinus rhythm after crossclamp removal were fewer in the WB group ( p = 0.03) (WB, 0.8 ± 0.3; CB, 4.0 ± 1.2; CC, 5.5 ± 1.5). In this model of acute global myocardial ischemia, continuous aerobic warm blood cardioplegia has important advantages over two widely used clinical hypothermic protection techniques.

Bucindolol, a beta blocker, decreased ventricular fibrillation and maintained mechanical function in a pig model of acute myocardial ischemia.

Bucindolol is a new beta blocker with marked vasodilatory properties and intrinsic sympathomimetic activity. We tested its potential effect against ventricular fibrillation (VF), in a pig model of acute myocardial ischemia. Bucindolol 6 mg/kg IV was administered in two equally divided doses, the first 30 minutes prior to, and the second 10 minutes after, ligation of the anterior descending coronary artery (CAL) in anesthetized open-chest pigs. Bucindolol decreased the incidence of VF to 1/11 versus 14/16 in the control group (p less than 0.005). Bucindolol also decreased the duration of ventricular tachycardia, 15 +/- 8 seconds versus 104 +/- 32 seconds in the control group (p less than 0.01). Bucindolol maintained LVmaxdP/dt at predrug and pre-CAL values, whereas LVmaxdP/dt was decreased by CAL in the control group. Bucindolol decreased arterial pressure and heart rate. Bucindolol increased blood flow in the peripheral ischemic zone (24.6 +/- 1.8% versus 16.2 +/- 1.7% (percent of pre-CAL value) in controls, p less than 0.002), as well as in the nonischemic zones (periischemic zone: 126.4 +/- 6.1% versus 96.7 +/- 4.8% in the control group, p less than 0.0005; remote nonischemic zone: 126.6 +/- 7.1% versus 87.1 +/- 4.3% of pre-CAL value in the control group, p less than 0.0001). Bucindolol had marked antiarrhythmic effects that were associated with beneficial effects on the mechanical function of the left ventricle and on blood flow to the ischemic myocardium.