Effects of adenosine and acadesine on interstitial nucleosides and myocardial stunning in the pig

1999 ◽  
Vol 77 (4) ◽  
pp. 259-267 ◽  
Author(s):  
Robert D Lasley ◽  
Mohinder PS Randhawa, Jr. ◽  
Julia O Hegge ◽  
Robert M Mentzer, Jr.
Keyword(s):  
Myocardial Stunning ◽  
Interstitial Fluid ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Ischemic Myocardium ◽  
Wall Thickening ◽  
Control Value ◽  
Cardioprotective Effects ◽  
Systolic Wall Thickening ◽  
Regional Ventricular Function

5-Amino-4-imidazolecarboxamide riboside (AICAr) or acadesine has been proposed to exert cardioprotection by enhancing adenosine production in ischemic myocardium. However, there are conflicting reports on acadesine's effects in ischemic myocardium and few studies in which myocardial adenosine levels have been measured. The purpose of this study was to determine whether acadesine increases interstitial fluid adenosine levels and attenuates myocardial stunning or potentiates the effects of adenosine in the intact pig. In pentobarbital-anesthetized pigs, myocardial stunning was induced by 10 min left anterior descending coronary artery occlusion and 90 min reperfusion. Regional ventricular function was assessed by measuring systolic wall thickening, and interstitial nucleosides were estimated by cardiac microdialysis. Control hearts were compared with hearts treated with acadesine, adenosine, and adenosine plus acadesine. Adenosine pretreatment (100 µg·kg-1·min-1, intracoronary) immediately prior to ischemia increased interstitial adenosine levels 9-fold and improved postischemic functional recovery from a control value of 17.6 ± 4.1% to 43.6 ± 3.4% of preischemic systolic wall thickening. In contrast, acadesine (20 mg/kg i.v. bolus 10 min prior to ischemia + 0.5 mg·kg-1·min-1, i.v. infusion through 60 min reperfusion) had no effect on interstitial fluid adenosine levels or the recovery of regional function (21.5 ± 5.9% recovery), nor were the functional effects of adenosine potentiated by acadesine. These findings indicate that acadesine does not enhance myocardial adenosine levels, attenuate myocardial stunning, or potentiate the cardioprotective effects of adenosine in the pig.Key words: adenosine, acadesine, interstitial fluid, microdialysis, myocardial stunning.

Differences in myocardial stunning following coronary artery occlusion in conscious dogs, pigs, and baboons

1996 ◽  
Vol 270 (4) ◽  
pp. H1312-H1322 ◽  
Author(s):  
Y. T. Shen ◽  
S. F. Vatner
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Stunning ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Conscious Dogs ◽  
Wall Thickening ◽  
Systolic Wall Thickening

To determine whether myocardial stunning differs among dogs, pigs, and baboons and is reproducible within species, we examined the effects of 10-min coronary artery (CA) occlusion (CAO) on 9 conscious dogs, 12 minipigs, and 6 baboons. During 10-min CAO, systolic wall thickening in the ischemic zone fell similarly in dogs (-108 +/- 5.6%), pigs (-102 +/- 1.8%), and baboons (-107 +/- 5.7%), but blood flow fell more (P < 0.05) in the subepicardium in pigs (0.07 +/- 0.01 ml.min-1.g-1) and baboons (0.07 +/- 0.02 ml.min-1.g-1) than in dogs (0.18 +/- 0.03 ml.min-1.g-1). At 1 h after CA reperfusion (CAR), wall thickening was reduced more (P < 0.05) in dogs (-40 +/- 4.2%) than in pigs (-22 +/- 2.1%) and baboons (-4 +/- 2.4%). In five dogs and five pigs, three separate 10-min CAO, each 2 days apart, were also examined. In dogs, reductions in wall thickening after CAR were significantly less following the second (-26 +/- 4.2%) or third (-30 +/- 3.2%) CAO, compared with the first CAO (-47 +/- 4.9%). In contrast, repetitive CAO did not induce differences in recovery of wall thickening in pigs. These results indicate that myocardial stunning is less severe in conscious pigs and baboons, compared with conscious dogs, despite more intense transmural ischemia. The dogs demonstrated a "preconditioning-like effect" with serial brief CAO, which was not exhibited in pigs.

Reduction in postsystolic wall thickening during late preconditioning

2007 ◽  
Vol 292 (1) ◽  
pp. H158-H164 ◽  
Author(s):  
Xavier Monnet ◽  
Laurence Lucats ◽  
Patrice Colin ◽  
Geneviève Derumeaux ◽  
Jean-Luc Dubois-Rande ◽  
...  
Keyword(s):  
Myocardial Stunning ◽  
Time Course ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Wall Thickening ◽  
Circumflex Artery ◽  
Late Preconditioning ◽  
Rapid Ventricular Pacing ◽  
Systolic Wall Thickening ◽  
Similar Decrease

Brief coronary artery occlusion (CAO) and reperfusion induce myocardial stunning and late preconditioning. Postsystolic wall thickening (PSWT) also develops with CAO and reperfusion. However, the time course of PSWT during stunning and the regional function pattern of the preconditioned myocardium remain unknown. The goal of this study was to investigate the evolution of PSWT during myocardial stunning and its modifications during late preconditioning. Dogs were chronically instrumented to measure (sonomicrometry) systolic wall thickening (SWT), PSWT, total wall thickening (TWT = SWT + PSWT), and maximal rate of thickening (dWT/d tmax). Two 10-min CAO (circumflex artery) were performed 24 h apart ( day 0 and day 1, n = 7). At day 0, CAO decreased SWT and increased PSWT. During the first hours of the subsequent stunning, evolution of PSWT was symmetrical to that of SWT. At day 1, baseline SWT was similar to day 0, but PSWT was reduced (−66%), while dWT/d tmax and SWT/TWT ratio increased (+48 and +14%, respectively). After CAO at day 1, stunning was reduced, indicating late preconditioning. Simultaneously vs. day 0, PSWT was significantly reduced, and dWT/d tmax as well as SWT/TWT ratio were increased, i.e., a greater part of TWT was devoted to ejection. Similar decrease in PSWT was observed with a nonischemic preconditioning stimulus (rapid ventricular pacing, n = 4). In conclusion, a major contractile adaptation occurs during late preconditioning, i.e., the rate of wall thickening is enhanced and PWST is almost abolished. These phenotype adaptations represent potential approaches for characterizing stunning and late preconditioning with repetitive ischemia in humans.

Mechanical Unloading Properties of Axial Flow Pumps and their Effect on Myocardial Stunning

1995 ◽  
Vol 18 (12) ◽  
pp. 766-771 ◽  
Author(s):  
F. R. Waldenberger ◽  
B. Meyns ◽  
P. Wouters ◽  
E. De Ruyter ◽  
E. Pongo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Myocardial Stunning ◽  
Myocardial Dysfunction ◽  
Axial Flow ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Wall Thickening ◽  
Myocardial Wall Motion ◽  
Mechanical Unloading ◽  
Artery Disease

Postischemic myocardial dysfunction affects morbidity and mortality in patients with coronary artery disease. It is known that mechanical unloading of the left heart ventricle can positively influence postischemic myocardial dysfunction. In this respect we tested two miniaturised axial flow pumps, i.e. the 14-F and the 21-F Hemopump®. An experimental study was carried out on 30 open chest sheep where regional myocardial wall motion was followed using sonomicrometry in a preparation of transient coronary artery occlusion. Only the larger 21-F Hemopump® showed hemodynamically significant unloading of the left ventricle. Furthermore, as far as stunning is concerned, systolic wall thickening recovered better when this type of pump was used during reperfusion. Also postejection thickening, which is an indication of diastolic postischemic dysfunction, is reduced significantly in the postischemic area (ANOVA, p<0.05). Thus, the 21F Hemopump®, but not the 14F Hemopump®, provides adequate mechanical unloading in order to beneficially influence myocardial stunning.

Mechanisms mediating responsiveness to beta-adrenergic stimulation after coronary reperfusion in conscious dogs

1994 ◽  
Vol 267 (4) ◽  
pp. H1578-H1588 ◽  
Author(s):  
K. Kiuchi ◽  
Y. T. Shen ◽  
S. F. Vatner ◽  
D. E. Vatner
Keyword(s):  
Adenylyl Cyclase ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Ischemic Myocardium ◽  
Regional Myocardial Blood Flow ◽  
Wall Thickening ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
High Affinity ◽  
Total Beta

The goal of this study was to assess beta-adrenergic receptor (beta-AR) signaling mechanisms in mediating physiological responses to sympathomimetic amines after 45 min coronary artery occlusion followed by 45 min reperfusion. At this time, isoproterenol (Iso) infusion (0.1 microgram/kg-1.min-1, n = 5) increased percent wall thickening in previously ischemic subendocardium (Endo) more than in nonischemic Endo (12.6 +/- 1.2 vs. 7.2 +/- 0.6%, P < 0.05), whereas forskolin (25 nmol.kg-1.min-1, n = 6) elicited the opposite effect (3.6 +/- 0.6 vs. 10.4 +/- 2.8%, P < 0.05). During Iso and forskolin infusions increases in regional myocardial blood flow in the previously ischemic zone were similar to the nonischemic zone. In all groups, total beta-AR density was depressed in previously ischemic Endo compared with nonischemic Endo (65 +/- 7 vs. 82 +/- 8 fmol/mg, P < 0.05), but the fraction of beta-AR binding agonist with high affinity increased (82 +/- 4 vs. 49 +/- 1%, P < 0.05). The changes in beta-AR were associated with a decrease in Iso-stimulated adenylyl cyclase (22 +/- 8%), a decrease in guanosine 5'-triphosphate (GTP)-stimulatory protein (Gs) (23 +/- 6%), and a decrease in inhibitory G proteins (16 +/- 4%). However, regional Endo functional responsiveness to beta-AR stimulation was enhanced in reperfused myocardium in response to Iso but not to forskolin. Thus the mechanism of increased number of beta-AR binding agonist with high affinity in previously ischemic myocardium predominated over persistent downregulation of total beta-AR density and reductions in Gs and adenylyl cyclase activity and correlated best with the physiological response to beta-AR stimulation. These data may also suggest that Iso exerts an action distal to adenylyl cyclase in previously ischemic myocardium.

Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits

2006 ◽  
Vol 291 (3) ◽  
pp. H1345-H1350 ◽  
Author(s):  
Nicolas Couvreur ◽  
Laurence Lucats ◽  
Renaud Tissier ◽  
Alain Bize ◽  
Alain Berdeaux ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Segment Length ◽  
Wall Thickening ◽  
Area At Risk

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO ( n = 5), 30 s CAR/30 s CAO ( n = 7), and 1 min CAR/1 min CAO ( n = 6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33 ± 4 vs. 34 ± 4%, 30 ± 4 vs. 30 ± 4%, and 33 ± 4 vs. 32 ± 4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39 ± 7%, n = 6 vs. 56 ± 4%, n = 7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.

Improved performance of ischemic canine myocardium in response to nifedipine and diltiazem

1980 ◽  
Vol 239 (5) ◽  
pp. H658-H663 ◽  
Author(s):  
J. E. Perez ◽  
B. E. Sobel ◽  
P. D. Henry
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Occlusion ◽  
Aortic Pressure ◽  
Artery Occlusion ◽  
Ischemic Myocardium ◽  
Control Value ◽  
Anesthetized Dogs ◽  
Improved Performance ◽  
Mean Aortic Pressure ◽  
Canine Myocardium

To characterize the effects of Ca2+ antagonists on the performance of the ischemic myocardium, we administered nifedipine and diltiazem to chloralose-anesthetized dogs with coronary artery occlusion and monitored segmental myocardial shortening in ischemic and nonischemic zones with implanted ultrasonic length gauges. Other dogs were treated with nitroglycerin or nitroprusside for comparison. Dosage of all drugs was adjusted to reduce mean aortic pressure by no more than 5 mmHg. Segmental shortening was expressed as percent of control value before occlusion. In control dogs (n = 8), shortening in ischemic zones 20 and 80 min after occlusion averaged -16 +/- 2% and -17 +/- 2%, indicating paradoxical elongation. With nifedipine (1 +/- 0.4 microgram . kg-1 . h-1; n = 8), shortening of ischemic segments before treatment did not differ from controls, but after 60 min of treatment was markedly improved, averaging 31 +/- 4% (P < 0.05). Diltiazem (10 +/- 2 microgram . kg-1 . h-1; n = 8) produced a similar improvement in shortening in ischemic zones. However, nitroglycerin (177 +/- 20 microgram . kg-1 . h-1; n = 8) and nitroprusside (43 +/- 10 microgram . kg-1 . h-1; n = 8) failed to improve shortening in ischemic regions. Thus, Ca2+ antagonists improved performance in ischemic zones, but nitroglycerin and nitroprusside did not.

Regional myocardial function and metabolism during acute coronary artery occlusion

1982 ◽  
Vol 242 (6) ◽  
pp. H980-H989 ◽  
Author(s):  
H. Kanaide ◽  
R. Yoshimura ◽  
N. Makino ◽  
M. Nakamura
Keyword(s):  
Coronary Artery ◽  
Oxygen Saturation ◽  
Fiber Optics ◽  
Myocardial Function ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Isolated Rat Heart ◽  
Wall Thickening ◽  
Regional Ischemia ◽  
Systolic Wall Thickening

Regional changes in myocardial function and oxidative metabolism during acute coronary artery occlusion were recorded spectrophotometrically by incorporating fiber optics in the isolated rat heart perfused by Langendorff's procedure. Oxygen saturation of myoglobin, reduction of cytochrome aa3, and the dynamic wall thickness of the left ventricle were continuously and concurrently measured from absorbancy increments at 581-592 nm, 605-630 nm, and 568-592 nm, respectively. In contrast to a gradual decrease in the extent of systolic wall thickening in anoxia, observed decreases in both the extent and the duration of systolic wall thickening and the appearance of a late systolic bulge occurred within 5 s after the onset of regional ischemia. After 10 s of both anoxia and regional ischemia, oxygen saturation of myoglobin decreased by 50%, but fluorescence of nicotinamide adenine dinucleotide remained at aerobic level which indicated that mitochondrial oxidative energy production might still be maintained. Thus early and pronounced dysfunction of the ischemic region appeared to precede a substantial loss of ATP production.

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