Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning

Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K+-dependent ATP (KATP) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 ± 14.3 vs. 38.3 ± 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion ( P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 ± 6% and 3 ± 5% in control and PerC, respectively ( P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group ( P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion ( P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a KATPchannel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.

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Effect of endurance training early or late after coronary artery occlusion on left ventricular remodeling, hemodynamics, and survival in rats with chronic transmural myocardial infarction.

Circulation ◽

10.1161/01.cir.89.1.402 ◽

1994 ◽

Vol 89 (1) ◽

pp. 402-412 ◽

Cited By ~ 64

Author(s):

P Gaudron ◽

K Hu ◽

R Schamberger ◽

M Budin ◽

B Walter ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Endurance Training ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Left Ventricular

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Myocardial infarction and ventricular fibrillation due to iatrogenic right coronary artery occlusion following tricuspid valve annuloplasty: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytaa328 ◽

2020 ◽

Author(s):

Shi Sum Poon ◽

Joseph George ◽

Daniel Obaid ◽

Pankaj Kumar

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Ventricular Fibrillation ◽

Tricuspid Valve ◽

Right Coronary Artery ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Left Ventricular ◽

Haemodynamic Instability ◽

Tricuspid Valve Annuloplasty

Abstract Background Iatrogenic right coronary artery (RCA) injury is a rare complication of tricuspid valve annuloplasty. Given that surgical intervention is increasingly favoured for tricuspid regurgitation, it is of great importance to recognize potential complications following tricuspid valve surgery. Case summary A 72-year-old man underwent surgical mitral and tricuspid valve repair. The early post-operative course was complicated by recurrent ventricular fibrillation episodes. Due to haemodynamic instability, a re-sternotomy and another cardiopulmonary bypass run were required. The patient subsequently underwent coronary angiography study which confirmed RCA occlusion. The occluded posterior left ventricular (PLV) branch was reopened by balloon angioplasty. However, despite multiple attempts it was not possible to pass a coronary guide wire into the posterior descending artery (PDA). An intravascular ultrasound examination revealed that the ostium of the PDA was compressed by external factors leaving a narrow slit-like appearance with no accessible lumen. Subsequently, a drug-eluting stent was placed into the PLV branch. The PDA was not accessible on repeated re-canalization attempts. The patient later successfully recovered from the right ventricular myocardial infarction. Discussion Right coronary artery occlusion should be considered as a differential diagnosis for significant rhythm disturbances and haemodynamic instability in the peri- and post-operative period following tricuspid valve annuloplasty. A low threshold for diagnostic angiography is needed to avoid potential delay in life-saving revascularization.

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Sevoflurane Reduces Myocardial Infarct Size and Decreases the Time Threshold for Ischemic Preconditioning in Dogs

Anesthesiology ◽

10.1097/00000542-199911000-00037 ◽

1999 ◽

Vol 91 (5) ◽

pp. 1437-1437 ◽

Cited By ~ 108

Author(s):

Wolfgang G. Toller ◽

Judy R. Kersten ◽

Paul S. Pagel ◽

Douglas A. Hettrick ◽

David C. Warltier

Keyword(s):

Coronary Artery ◽

Infarct Size ◽

Ischemic Preconditioning ◽

Myocardial Infarct ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Left Ventricular ◽

Myocardial Infarct Size ◽

Myocardial Ischemia And Reperfusion ◽

Time Threshold

Background Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (K(ATP)) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction. Methods Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the K(ATP) channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively. Results Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%). Conclusion Sevoflurane reduces myocardial infarct size by activating K(ATP) channels and reduces the time threshold for ischemic preconditioning independent of hemodynamic effects in vivo.

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Myocardial infarction with and without reperfusion in sheep: early cardiac and neurohumoral changes

Clinical Science ◽

10.1042/cs0980703 ◽

2000 ◽

Vol 98 (6) ◽

pp. 703-711 ◽

Cited By ~ 10

Author(s):

Christopher J. CHARLES ◽

John M. ELLIOTT ◽

M. Gary NICHOLLS ◽

Miriam T. RADEMAKER ◽

Mark RICHARDS

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Ejection Fraction ◽

Troponin T ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Left Ventricular ◽

Lv Function ◽

Large Animal ◽

Lv Dysfunction

There are few stable and reproducible large-animal models of chronic heart failure produced by ischaemic damage to the myocardium. Here we characterize a novel method of inducing myocardial damage in closed-chest sheep by catheter delivery of thrombogenic coils, and compare this with a newly described open-artery model of cardiac injury in sheep. Sham controls were compared with animals subjected to (a) 90 min of coronary artery occlusion/reperfusion by PTCA (percutaneous transluminal coronary angioplasty) balloon, and (b) permanent coronary artery occlusion induced by catheter delivery of thrombogenic coils (seven sheep/group). Both balloon occlusion/reperfusion and permanent coil occlusion resulted in well-defined anteroapical infarcts, as documented by ECG changes, significant rises in creatine kinase (both groups P < 0.001) and troponin-T (both groups P < 0.05), and post-mortem examination. Washout of enzymes was much more rapid in the reperfused group (P < 0.01). Infarction resulted in significant reductions in left ventricular (LV) ejection fraction (both groups P < 0.01) and regional wall abnormalities. Ejection fraction 7 days post-coil (21.3±4.2%) was significantly lower (P < 0.01) than that 7 days post-balloon (38.8±4.5%). Coil-induced infarction was associated with acutely reduced arterial pressure (P < 0.05), and increases in heart rate (P < 0.05), atrial pressures (P < 0.05), plasma brain natriuretic peptide levels (P < 0.05) and adrenaline levels (P < 0.05). Rises seen in plasma endothelin levels in sham controls were blunted in the coil group (P < 0.001). Haemodynamic changes were less marked in the balloon group. In conclusion, restriction of coronary artery occlusion to 90 min results in infarction, but less LV dysfunction with reduced early remodelling, compared with permanent occlusion. Acute changes in biochemical markers, haemodynamics, neurohormones and LV function confirm that these are excellent models of open- and closed-artery myocardial infarction leading to asymptomatic LV dysfunction.

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Ketamine, but Not S (+)-ketamine, Blocks Ischemic Preconditioning in Rabbit Hearts In Vivo

Anesthesiology ◽

10.1097/00000542-200104000-00017 ◽

2001 ◽

Vol 94 (4) ◽

pp. 630-636 ◽

Cited By ~ 62

Author(s):

Jost Müllenheim ◽

Jan Fräßdorf ◽

Benedikt Preckel ◽

Volker Thämer ◽

Wolfgang Schlack

Keyword(s):

Cardiac Output ◽

Coronary Artery ◽

Infarct Size ◽

Ischemic Preconditioning ◽

Left Ventricular Pressure ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Left Ventricular ◽

Ventricular Pressure

Background Ketamine blocks KATP channels in isolated cells and abolishes the cardioprotective effect of ischemic preconditioning in vitro. The authors investigated the effects of ketamine and S(+)-ketamine on ischemic preconditioning in the rabbit heart in vivo. Methods In 46 alpha-chloralose-anesthetized rabbits, left ventricular pressure (tip manometer), cardiac output (ultrasonic flow probe), and myocardial infarct size (triphenyltetrazolium staining) at the end of the experiment were measured. All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. The control group underwent the ischemia-reperfusion program without preconditioning. Ischemic preconditioning was elicited by 5-min coronary artery occlusion followed by 10 min of reperfusion before the 30 min period of myocardial ischemia (preconditioning group). To test whether ketamine or S(+)-ketamine blocks the preconditioning-induced cardioprotection, each (10 mg kg(-1)) was administered 5 min before the preconditioning ischemia. To test any effect of ketamine itself, ketamine was also administered without preconditioning at the corresponding time point. Results Hemodynamic baseline values were not significantly different between groups [left ventricular pressure, 107 +/- 13 mmHg (mean +/- SD); cardiac output, 183 +/- 28 ml/min]. During coronary artery occlusion, left ventricular pressure was reduced to 83 +/- 14% of baseline and cardiac output to 84 +/- 19%. After 2 h of reperfusion, functional recovery was not significantly different among groups (left ventricular pressure, 77 +/- 19%; cardiac output, 86 +/- 18%). Infarct size was reduced from 45 +/- 16% of the area at risk in controls to 24 +/- 17% in the preconditioning group (P = 0.03). The administration of ketamine had no effect on infarct size in animals without preconditioning (48 +/- 18%), but abolished the cardioprotective effects of ischemic preconditioning (45 +/- 19%, P = 0.03). S(+)-ketamine did not affect ischemic preconditioning (25 +/- 11%, P = 1.0). Conclusions Ketamine, but not S(+)-ketamine blocks the cardioprotective effect of ischemic preconditioning in vivo.

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