Dl Brutsaert

Does endocardial endothelium mediate positive inotropic response to angiotensin I and angiotensin II

The positive inotropic response to angiotensin I and II in cardiac tissue of most mammalian species, as well as the exact site in the heart for conversion of local and systemic angiotensin I into angiotensin II, remains to be elucidated. In isolated cat papillary muscles, angiotensin I and angiotensin II (0.1 nM to 1 microM, 35 degrees C, 1.25 mM Ca2+) increased, in a dose-dependent manner, peak twitch tension with typical slight prolongation of twitch duration. This typical response did not necessitate the presence of an intact endocardial endothelium (EE), as a similar response was observed in muscles where the EE had been damaged by a 1-second exposure to 0.5% Triton X-100. After addition of captopril, an angiotensin converting enzyme inhibitor, the positive inotropic response to angiotensin I was completely abolished, both in the presence and the absence of an intact EE. Hence, the heart possesses angiotensin converting enzyme, which mediates the positive inotropic response to angiotensin I. An intact EE was not a prerequisite for this response; thus, myocytes as well as nonmyocytes may be possible locations (in addition to the EE) for angiotensin converting enzyme. In the presence of an intact EE, and after addition of captopril, the positive inotropic response to angiotensin II was significantly diminished (desensitization). By contrast, in the absence of an intact EE, but also after addition of captopril, the positive response to angiotensin II was potentiated (sensitization). Both desensitization and sensitization (in the presence or absence of an intact EE, respectively) of the response to angiotensin II induced by the addition of captopril were inhibited by indomethacin, a cyclooxygenase inhibitor, suggesting a role for prostaglandins.

Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium

Irradiation of isolated cardiac muscle by high-power, high-frequency, continuous wave ultrasound selectively damages endocardial endothelium (EE). We evaluated this ultrasound effect in vivo on the performance of the intact ejecting canine left ventricle (LV). A cylindrical ultrasound probe (0.9 MHz, 25 W), mounted on a catheter, was inserted in the LV cavity through an apical stab wound and was activated for 60, 120, and 240 s, followed each time by a recovery period of 10-15 min. Ultrasound transiently and repeatedly abbreviated the time interval from end diastole to peak (-)dP/dt (from 241 +/- 30 to 229 +/- 32 ms after 240 s; P < 0.001), accelerated LV pressure fall, did not alter peak (+)-dP/dt or peak systolic pressure, increased diastolic and systolic segment lengths, and decreased fractional shortening. Microscopic analysis revealed dispersed granulocytes attached to the EE. EE cells were visibly damaged only in a limited area surrounding the probe. Accordingly, high-power, high-frequency, continuous wave ultrasound reversibly modulated LV performance, presumably by transient alteration of EE function.

Myocardial inotropic responses to aggregating platelets and modulation by the endocardium.

Ventricular mural thrombi complicate many cardiac diseases. The endocardial endothelium can modulate the mechanical performance of subjacent myocardium and mediate responses to certain physiopharmacologic agents. We studied the effects of aggregating platelets on the contractile performance of isolated cardiac muscle. The role of the endocardium was investigated by selectively damaging it by very brief (1 second) exposure to 1% Triton X-100 in some muscle preparations before experiments. Cat papillary muscles (n = 54) were attached to an electromagnetic length-tension transducer in organ baths containing Krebs-Ringer solution (1.25 mM Ca2+, 35 degrees C), and stimulated electrically at 0.2 Hz. Homologous washed platelets (final concentration 3 x 10(11)/l) aggregated spontaneously on addition to baths. Mechanical performance increased significantly more in muscles with damaged endocardium than in intact muscles (p less than 0.05); total peak isometric twitch tension increased by 31.8 +/- 7.8% (with damaged endocardium) and 11.8 +/- 2.6% (with intact endocardium), and peak isotonic twitch shortening increased by 36.7 +/- 7.8% (with damaged endocardium) and 9.6 +/- 2.0% (with intact endocardium). Increases in maximum velocity of unloaded shortening were similar in both muscle groups. Time to half isometric twitch tension decline decreased in intact muscles (3.6 +/- 1.0%) but increased in Triton-treated muscles (2.5 +/- 1.3%, p = 0.003 for difference between groups). The inotropic response to platelets in muscles with intact endocardium was unaltered by pretreatment of muscles with indomethacin (10 microM) or by stimulation of platelet aggregation with thrombin (0.1 unit/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha 1-adrenergic stimulation.

Background. High‐power intracavitary ultrasound abbreviates left ventricular (LV) ejection duration, thereby decreasing mechanical LV performance, presumably by selective impairment of endocardial endothelial function. Methods and Results. Effects of ultrasound were evaluated in the ejecting LV of anesthetized, open‐chest dogs under different conditions of LV volume and contractile state and after mild selective &agr;1‐adrenergic stimulation. LV pressures, left atrial pressures, and regional segment lengths were measured in anterior and posterior midwall. A cylindrical ultrasound probe (0.9 MHz, 25 W) mounted on a catheter was inserted into the LV cavity through the apex and was activated for 4 minutes in each condition. In protocol A (n=7), LV volume was altered with caval vein occlusion and intravenous dextran infusion. The ultrasound probe was activated at low (4.1±0.9 mm Hg), mid (10.6±1.5 mm Hg), and high (17.9±1.8 mm Hg) LV end‐diastolic pressure (EDP). Effects of ultrasound were less pronounced at higher EDP. For example, the time interval from end‐diastole to peak (−)dP/dt decreased by 7.5±2.3% at low, 4.4±2.2% at mid, and 1.9±1.6% at high LVEDP (p<0.001). In protocol B (n=7), LV inotropic state was altered by slow intravenous infusion of low‐dose calcium. The ultrasound probe was activated before and after calcium. Effects of ultrasound were less pronounced after calcium. Time from end‐diastole to peak (‐)dP/dt decreased by 8.4±3.1% at baseline and by 3.5±2.1% after calcium (p<0.001). In protocol C (n=7), activation of the ultrasound probe was performed at baseline and after mild selective &agr;1‐adrenergic stimulation (propranolol plus phenylephrine). Effects of ultrasound were similar at baseline and after propranolol but increased after phenylephrine. Time from end‐diastole to peak (‐)dP/dt decreased by 5.2±2.4% at baseline, by 5.3±1.9% after propranolol, and by 8.9±3.2% after phenylephrine (p<0.05). Conclusions. Effects of intracavitary ultrasound, which are presumably mediated through modulation of endocardial endothelial function, were more important at low volume, lower calcium, and under mild selective &agr;1‐adrenergic stimulation. (Circulation 1993;87:1275‐1285)