Effect of dysfunctional vascular endothelium on myocardial performance in isolated papillary muscles.

Abstract

Vascular endothelium has been shown to modify the contractile characteristics of vascular smooth muscle, and endocardial endothelium has been shown to modify the contractile characteristics of adjacent myocardium. In this study, whether vascular endothelium also modifies the contractile characteristics of adjacent myocardium and whether these effects are additive to those of endocardial endothelium were investigated. Rabbit hearts (n=54) were excised and mounted in a Langendorif preparation. Vascular reactivity was verified by acetylcholine infusion. One group of these hearts had Triton X-100 injected as a bolus into the coronaries to render the vascular endothelium dysfunctional. The other portion served as control hearts. Triton X-100 bolus injection resulted in little or no pathological changes on morphological examination; however, the vasodilatory response to acetylcholine in these hearts was abolished, suggesting vascular endothelial dysfunction. Vascular smooth muscle reactivity was verified in Triton X-100-injected hearts by nitroprusside infusion. In the control Langendorff-perfused hearts, there was little evidence of vascular endothelial dysfunction, with the coronary perfusion rate increasing from 8.9±0.4 to 11.0±0.3 ml/g per minute (p<0.01) in response to acetylcholine. All hearts were then removed, and right ventricular papillary muscles were excised for myocardial mechanical studies. Control Langendorffperfused hearts had myocardial mechanical characteristics similar to those of muscles from 18 other control hearts without Langendorff perfusion, indicating that the Langendorff perfusion itself had little effect on myocardial mechanics. The muscles from the Triton X-100-injected Langendorff hearts had marked changes: a shortening of twitch duration (363± 16 versus 449±9 msec, p<0.01) and decreases in total tension (2.2±0.2 versus 2.9±0.2 g/mm2, p<0.01), dT/dt (9±1 versus 12±1 g/mm2 per second, p<0.05), and maximum velocity of unloaded muscle shortening (Vmax) (0.89±0.06 versus 1.14±0.07 length at which maximum developed tension occurred [Lm.]/sec, p<0.05). Endocardial endothelial removal of the papillary muscles in the two control groups (with and without Langendorif perfusion) by Triton X-100 caused the same changes in twitch characteristics as occurred in muscles from the Langendorff-perfused hearts injected with Triton X-100 but with intact endocardial endothelium, suggesting that vascular endothelial dysfunction had similar effects on contractile characteristics as endocardial endothelial removal. Endocardial endothelial removal of the papillary muscles from Langendorif-perfused hearts that had a bolus injection of Triton X-100 caused further shortening of twitch duration and a further decrease in total tension (1.7±0.2 versus 2.1±0.1 g/mm2, p<O.05), dT/dt, and Vmax (0.69±0.03 versus 0.89±0.01 L,../sec, p<O.01), suggesting that the myocardial contractile effects of endocardial and vascular endothelium are additive. Increasing extracellular calcium concentration to 15 mM normalized dT/dt and Vm....

Destruction of Contrast Microbubbles by Ultrasound

“…17 Other investigators have shown that similar dysfunction could be obtained by selectively damaging the endothelial monolayer of the coronary bed. 18 At variance with these earlier reports, in the present study, exposure of hearts to ultrasound alone, even at an MI of 1.6, did not produce any LV contractile dysfunction. This is probably because the energy levels used in the present study were considerably lower than those used in the previous reports.…”

Activation of Cardiac Endothelium as a Compensatory Component in Endotoxin-Induced Cardiomyopathy

“…In vitro and in vivo studies have shown that cardiac endothelium and its paracrine mediators (NO, PGs, ET-1, and other as yet unidentified agents) alter myocardial contractile performance mainly by influencing the time of onset of relaxation, primarily via changes in cardiac myofilament response to calcium. 3,[17][18][19] Consistently, the presented mechanical analysis revealed marked changes in the onset of A, Change in contractile performance parameters (meanϮSEM) from baseline by the combination of the 3 inhibitors of endothelial factors L-NMMA, BQ-123, and indomethacin in papillary muscles from 3 groups of rabbits (control, LPSϩ12h, and LPSϩ36h). B, Change in tHR (ms) from baseline by inhibition of either NO, ET-1, or PG pathways.…”

Cytostatic Drugs, Neuregulin Activation of ErbB Receptors, and Angiogenesis

“…Cardiac endothelial cells (vascular and endocardial) are uniquely poised to act as sensors of systemic stress (by virtue of exposure to circulating factors) as well as sensors and regulators of cardiac stress and function (by virtue of their close proximity to cardiac myocytes). The idea that cardiac endothelial cells play a critical role in autocrine/ paracrine regulation of the heart is supported by the finding that removal of either of these types of endothelial cells has significant detrimental effects on the contractile function of the adjacent cardiac myocytes [35]. Despite these important observations, the mechanisms and mediators of these functions of the endothelial cells are largely undefined.…”

“…In addition to the obviously critical role of supplying oxygen and nutrients to the myocardium, vascular endothelium plays a critical role in maintaining myofilament integrity and myocyte contractility [35]. The relationship between cardiac growth and capillary density has revealed some fascinating concepts demonstrating a tight interrelationship between myocardial and vascular mass in the normal heart, and dysregulation of this relationship in disease states [38].…”