Vasospasm of Atherosclerotic Coronary Arteries Precipitates Acute Ischemic Myocardial Damage in Myocardial Infarction–Prone Strain of the Watanabe Heritable Hyperlipidemic Rabbits

Abstract

Objective This study tested the hypothesis that vasospasm can trigger of coronary plaque injury and acute ischemic myocardial damage. Approach and Results Hyperlipidemic myocardial infarction–prone rabbits (WHHLMI strain) received an intravenous bolus of ergonovine maleate (0.45 μmol/kg) during intravenous infusion of norepinephrine (12 nmol/kg/min) to provoke coronary spasm in vivo. After this treatment, coronary angiography demonstrated vasospasm, and the electrocardiogram (ECG) showed ischemic abnormalities (ST depression/elevation and T-wave inversion) in 77% of animals (23/30). These changes normalized after nitroglycerin injection. In rabbits that demonstrated these ECG findings for more than 20 minutes, echocardiograms showed left ventricular wall motion abnormality. Serum levels of heart-type fatty acid binding protein, cardiac troponin-I, and myoglobin increased markedly 4 hours after spasm provocation. In coronary lesions of WHHLMI rabbits with provoked coronary spasm, we observed intimal injury in 60.9% in the form of endothelial cell protrusions (39.1%), denudation (30.4%), and macrophage extravasation (56.5%). Plaque disruption with luminal thrombus, however, was only seen in 2/23 animals (8.7%), and mural microthrombus was rarely observed (4.3%). Conclusions These observations show that provocation of vasospasm in WHHLMI rabbits associates with subsequent ischemic myocardial damage. Although treatment with spasmogens altered aspects of plaque morphology, for example endothelial protrusion and macrophage emigration, thrombosis was rare in these animals with chronic atherosclerotic disease.

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease

“…Few established experimental approaches described in animals aim to mimic aspects of spontaneous luminal thrombus formation on stable atherosclerotic plaques. 102 …”

High Susceptibility of Atherosclerotic Coronary Arteries to the Onset of Vasospasm and Angina Pectoris-like Symptoms due to Coronary Spasm in WHHLMI Rabbits

“…The provocation and evaluation of coronary spasm were performed as previously described [20], and the study design was shown in Figure 1.…”

“…Echocardiograms were performed using 13 WHHLMI rabbits and 7 JW rabbits with a Philips Envisor C echocardiograph (Philips Inc., Eindhoven and the Netherlands) [20]. Left …”

“…We here in reanalyzed the data of our study [20] with the addition of data from four extra rabbits and ex vivo coronary contraction experiments to determine whether the severity of coronary plaques affected provocation of coronary spasm and acute ischemic myocardial events in WHHLMI rabbits.…”

“…We previously provoked coronary spasm in WHHLMI rabbits and demonstrated the associations between of coronary spasm and plaque disruption as well as ischemic myocardial damage [20]. However, we did not sufficiently examine the effects of coronary plaques on the provocation of coronary spasm or development of angina pectoris- …”