It takes time to heal a broken heart: Ventricular plasticity improves heart performance after myocardial infarction in rainbow trout, Oncorhynchus mykiss

Coronary arteriosclerosis is a common feature of both wild and farmed salmonid fishes and may be linked to stress-induced cardiac pathologies. Yet, the plasticity and capacity for long-term myocardial restructuring and recovery following a restriction in coronary blood supply is unknown. Here, we analyzed the consequences of acute (3 days) and chronic (from 33 to 62 days) coronary occlusion (i.e., coronary artery ligation) on cardiac morphological characteristics and in vivo function in juvenile rainbow trout, Oncorhynchus mykiss. Acute coronary occlusion resulted in elevated resting heart rate and decreased inter-beat variability, which are both markers of autonomic dysfunction following acute myocardial ischemia, along with severely reduced heart rate scope (maximum – resting heart rate) relative to sham-operated trout. We also observed a loss of myocardial interstitial collagen and compact myocardium. Following long-term coronary- ligation, resting heart rate and heart rate scope normalized relative to sham-operated trout. Moreover, a distinct fibrous collagen layer separating the compact myocardium into two layers had formed. This may contribute to maintain ventricular integrity across the cardiac cycle, or alternatively, demark a region of the compact myocardium that continues to receive oxygen from the luminal venous blood. Taken together, we demonstrate that rainbow trout may cope with the aversive effects caused by coronary artery obstruction through plastic ventricular remodeling, which, at least in part, restores cardiac performance and myocardium oxygenation.

Mechanism and Potential Treatment of the 'No Reflow' Phenomenon After Acute Myocardial Infarction: Role of Pericytes and GPR39

The 'no reflow' phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow, and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, prior to reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared to controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39 knockout and VC43 treated mice compared to controls. We conclude that GPR39 mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI, and that smaller no reflow zones in GPR39 knockout and VC43 treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI as well as providing a therapeutic pathway for the condition.