Circulation research
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Circulation research · Jun 1992
Comparative StudyRight ventricular preload recruitable stroke work, end-systolic pressure-volume, and dP/dtmax-end-diastolic volume relations compared as indexes of right ventricular contractile performance in conscious dogs.
Three indexes developed originally to assess left ventricular contractile performance were applied instead to the right ventricle (RV) in 11 conscious dogs: the relation between stroke work and end-diastolic volume (EDV), termed the preload recruitable stroke work (PRSW) relation; the end-systolic pressure-volume (ESPV) relation; and the maximum dP/dt (dP/dtmax)-EDV relation. The reproducibility, inotropic sensitivity, chronotropic sensitivity, and afterload sensitivity of these RV relations were compared. RV volume was determined with an ellipsoidal shell subtraction model from orthogonal dimensions measured by sonomicrometry. ⋯ Despite a 71 +/- 26% increase in mean RV ejection pressure during partial occlusion of the main pulmonary artery, the slopes and volume-axis intercepts of both the PRSW and dP/dtmax-EDV relations did not change significantly, but the slope of the ESPV relation increased 45 +/- 22% (p less than 0.05) without significant change in the volume-axis intercept. None of the relations demonstrated significant chronotropic sensitivity. The PRSW relation is the preferred index of RV contractile performance because 1) it is the most reproducible, 2) its slope alone sensitively detects changes in contractile state, and 3) unlike the ESPV relation, it is relatively insensitive to afterload.
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Circulation research · Sep 1991
Comparative StudyBlockade of cardiac sodium channels by amitriptyline and diphenylhydantoin. Evidence for two use-dependent binding sites.
Cardiac toxicity is a frequent manifestation in amitriptyline overdose and is felt to be due, in part, to sodium channel blockade by the drug. Another agent with sodium channel blocking properties, diphenylhydantoin, has been used clinically to reverse cardiac conduction abnormalities induced by amitriptyline. This reversal of toxicity is believed to occur secondary to competition for the sodium channel binding site. ⋯ Conversely, when pHi was increased from 7.3 to 8.0, tau r after amitriptyline was unaffected, but tau r after diphenylhydantoin markedly increased (from 0.71 +/- 0.21 to 2.60 +/- 1.30 seconds, p less than 0.001). Additionally, diphenylhydantoin block demonstrated profound voltage dependence across the range of -130 to -90 mV, whereas amitriptyline block appeared less voltage sensitive. Single-channel studies using patch-clamp techniques in isolated ventricular myocytes supported these data.(ABSTRACT TRUNCATED AT 400 WORDS)
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Circulation research · Sep 1991
Comparative StudyEndothelin 1 enhances myofilament Ca2+ responsiveness in aequorin-loaded ferret myocardium.
The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of both aequorin light signals (maximum, 31 +/- 12%) and developed tension (maximum, 64 +/- 13%). The peak aequorin light [( Ca2+]i)-peak tension curve generated by increasing endothelin concentrations was steeper and shifted to the left of the curve generated by varying [Ca2+]o; however, the maximum developed tension produced by endothelin did not exceed that produced by 6 mM [Ca2+]o. ⋯ Moreover, 1 x 10(-7) M endothelin caused an upward shift in the peak aequorin light-peak tension curve generated by varying [Ca2+]o and increased the maximum twitch force by about 12%. The contractions were prolonged, whereas the time course of the Ca2+ transient was not changed in the presence of endothelin. When the function of the sarcoplasmic reticulum was inhibited by 6 microM ryanodine, 10(-7) M endothelin still increased the force generation without increasing the intracellular peak Ca2+, either during isometric twitches or during tetani.(ABSTRACT TRUNCATED AT 250 WORDS)
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Circulation research · Aug 1991
Comparative StudyEffects of MK-801 on cerebral regional oxygen consumption in focal cerebral ischemia in rats.
This investigation tested in rats whether MK-801, an N-methyl-D-aspartate receptor antagonist, would improve the balance of oxygen supply and consumption in the focal ischemic area of the brain induced by occlusion of the middle cerebral artery. Fifteen minutes after middle cerebral artery occlusion, 5 mg/kg MK-801 was administered intravenously to the MK-801 group (n = 12), and normal saline was given to the control group (n = 12). One hour after the occlusion in each group, regional cerebral blood flow was determined in six rats using [14C]iodoantipyrine, and regional arterial and venous oxygen saturations were determined using a microspectrophotometric technique in the other six rats. ⋯ However, for the MK-801 group, there was no significant difference between the ischemic cortex (6.1 +/- 1.0) and the contralateral cortex (5.7 +/- 1.1). Oxygen extraction in the ischemic cortex of the MK-801 group was significantly lower than that of the control group. Calculated ischemic regional oxygen consumption was similar to the nonischemic values in the control group, whereas the ischemic value was reduced to 61% of the value of the contralateral cortex in the MK-801 group.(ABSTRACT TRUNCATED AT 250 WORDS)
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Circulation research · May 1991
Comparative StudyCarotid sinus baroreceptor reflex in dogs with experimental heart failure.
We have previously demonstrated a decrease in baroreceptor discharge sensitivity in dogs with experimental heart failure. In the present study, we determined the sensitivity of the carotid sinus baroreceptor reflex in dogs with pacing-induced heart failure. The carotid sinus baroreceptor reflex sensitivity was determined by pressurizing one carotid sinus with all other baroreceptor and cardiopulmonary receptor inputs removed. ⋯ As was the case with carotid sinus pressurization, electrical stimulation caused a significantly smaller change in mean arterial pressure in heart-failure dogs compared with the normal dogs. However, there was no significant difference between normal and heart-failure dogs for the renal sympathetic nerve activity-electrical stimulation curves. These data strongly suggest that the depressed carotid sinus baroreceptor reflex in heart failure is not solely the result of depressed baroreceptor responsiveness but may be related to poor end-organ responses and normal central control of renal sympathetic outflow.