Bradykinin increases myocardial contractility: relation to the Gregg phenomenon

Abstract

Bradykinin (BK) is reportedly produced in the heart during ischemia. Because BK has been shown to activate cardiac afferent nerves thought to be nocioceptors, we tested whether BK might alter myocardial shortening, which potentially could contribute to afferent nerve stimulation. In open-chest dogs, BK (1-10 micrograms) was injected into the left anterior descending (LAD) coronary artery while wall motion in the LAD and control circumflex regions was monitored. Wall motion was measured with midwall segment gauges (sonomicrometer crystals) placed in the hoop direction. Blood pressure, heart rate, left ventricular pressure, first derivative of left ventricular pressure, and LAD coronary flow also were monitored. At 15-20 s after injection, which was before circulation of the peptide caused blood pressure to change, BK decreased maximum end-diastolic and minimum end-systolic segment lengths and increased maximum shortening fraction in LAD region. No change was observed in circumflex region. The response was not eliminated by bilateral vagotomy or subsequent stellate ganglionectomy, indicating that it was not neurally mediated. The response closely paralleled changes in coronary flow, was mimicked by intracoronary injection of adenosine, and was reduced or absent if flow was already elevated by previous injection of adenosine. When BK eventually reached the systemic circulation, the resultant hypotension further reduced shortening in LAD region, with directionally similar effect in circumflex region. These results suggest that BK can increase regional shortening by enhancing coronary flow (Gregg phenomenon) as well as by altering global ventricular function through systemic hypotension. Such changes in shortening may contribute to stimulation of cardiac afferent nerves.