Delayed Reperfusion—Coronary Artery Reperfusion Close to Complete Myocardial Necrosis Benefits Remote Myocardium and Is Enhanced by Exercise

Abstract

The present study aimed to analyze the effects of reperfusion of a distant coronary artery on cardiac function, the ultrastructure, and the molecular environment of the remote myocardium immediately after the completion of myocardial regional necrosis: delayed reperfusion (DR). Additionally, the effects of prior exercise on the outcomes of DR were investigated. Female rats with permanent occlusion or delayed reperfusion were randomly assigned to an exercise (swimming, 1 h/day, 5 days/week for 8 weeks) or sedentary protocol. Thus, the study included the following four groups: sedentary permanent occlusion, exercise permanent occlusion, sedentary delayed reperfusion, and exercise delayed reperfusion. The descending coronary artery was occluded for 1 h. Reperfusion was confirmed by contrast echocardiography, and the rats were observed for 4 weeks. Permanent occlusion and DR caused similar myocardial infarction sizes among the four groups. Interestingly, exercise significantly decreased the mortality rate. Delayed reperfusion resulted in significant benefits, including enhanced hemodynamics and papillary muscle contraction, as well as reduced apoptosis and collagen content. Protein calcium kinetics did not change. Meanwhile, developed tension and the Frank–Starling mechanism were enhanced, suggesting that calcium sensitivity was intensified in myofilaments. Remarkable remote myocardial benefits occurred after distant DR, and prior exercise intensified cardiac recovery. Our findings provide valuable information about DR. Our data might explain the better clinical outcomes in recent studies showing that late reperfusion could improve heart failure in patients with myocardial infarction. In conclusion, DR has remote myocardial benefits, including inotropism enhancement, pulmonary congestion reduction, and collagen and apoptosis attenuation, which are enhanced by prior exercise.

Exercise training and experimental myocardial ischemia and reperfusion: A systematic review and meta-analysis

“…Table 2 presents sample characteristics (size, number of groups and animals per group) and exercise protocol (exercise type and intensity, session duration and frequency, and training and detraining duration). The exercise protocols included forced swimming [15] , [16] , [17] , [18] , resistance exercise [19] , and running training [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , being some few exercise protocols were voluntary [17] , [39] , [32] . Table 2 also reports the I/R procedures (ischemia and reperfusion duration until sacrifice, and dependent variables evaluated.…”

“…Regarding the infarct size, although it has been measured in 22 studies by various techniques (i.e. echocardiogram, tetrazolium, or risk area by Evans Blue), 20 have shown that exercise led to smaller infarct sizes [15] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [29] , [28] , [34] , [35] , [36] , [37] , [38] , [32] , [31] and only two studies did not report differences between exercised versus non-exercised animals [16] , [19] . Heart-to-body weight index was accessed by 13 studies, of which 12 articles reported increased in this indication of cardiac hypertrophy [17] , [18] , [20] , [23] , [27] , [36] , [38] , [29] , [30] , [31] .…”

“…Cardiac function parameters also were significantly improved in exercised groups reported by the selected studies. Left ventricular systolic and diastolic pressures as well as positive and negative pressure derivatives were increased by exercise in 8 of the 9 studies that evaluated ventricular hemodynamics [16] , [19] , [21] , [24] , [25] , [30] , [36] ; and ejection fraction was improved in 5 of the 6 studies that performed transthoracic echocardiography [17] , [21] , [26] , [27] , [32] indicating functional benefits of physical exercise in I/R. When arrhythmias were evaluated as an outcome (6 studies), all authors reported reduction on the post-I/R arrhythmias [22] , [31] , [32] , [33] , [34] , [38] .…”

“…Regarding the potential mechanisms involved in the benefits of exercise for I/R injury, all 12 studies that accessed oxidative stress reported reduction on this variable due to exercise [21] , [22] , [23] , [27] , [34] , [36] , [38] , [32] , [31] , [33] , [19] ; 2 of the 2 studies indicated improved cardiac mitochondrial function [36] , [19] ; and 6 of the 7 studies reported mitigation of apoptosis on the myocardium [15] , [16] , [17] , [30] , [34] , [38] while only one study showed no effect [40] . Finally, in regard of pathological changes on the gene/protein expression with I/R, all 20 studies that evaluated molecular remodeling [15] , [16] , [17] , [18] , [20] , [23] , [24] , [25] , [26] , [27] , [29] , [30] , [32] , [34] , [36] , [37] , [38] , [39] reported a beneficial profile in exercised compared with non-exercised groups.…”

Hypertrophy of the right ventricle by pulmonary artery banding in rats: a study of structural, functional, and transcriptomics alterations in the right and left ventricles

“…Pulmonary and systemic tissue congestions were measured, respectively ( Nozawa et al, 2006 ; Veiga et al, 2019 ). After euthanizing the animals, the right lung was isolated by stitching cotton thread around the pulmonary hilum.…”