Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maximal changes in haemodynamics and segmental wall motion were seen 2 min after coronary occlusion and were examined in relation to the loading conditions of the left ventricle before occlusion in 20 open chest dogs. There was a significant inverse relationship between the preligation mean aortic pressure and the percentage decrease in stroke volume following ligation. This relationship was observed whether afterload was distributed randomly (mean aortic pressure ranging from 9.7 to 17.6 kPa [73 to 132 mmHg]) between all dogs (r = 0.65; P less than 0.001) or altered by methoxamine (+4 kPa [+30 mmHg]) and nitroprusside (-3.2 kPa [-24 mmHg]) within the same dog (r = 0.82; P less than 0.001; n = 8). Although occlusion of the anterior descending artery caused a small (+5.5%) but significant increase in end-diastolic length of the non-ischaemic epicardial segment, the capacity for compensatory ventricular dilatation was not dependent on preligation afterload. However, the capacity of the ischaemic segment to undergo systolic expansion was significantly greater (+30.2% of end-systolic segment length) in those dogs with the lowest preligation MAP (8 to 12 kPa [60 to 90 mmHg]) compared with systolic lengthening of only 15.8% in the high afterload group (15 to 18 kPa [112 to 135 mmHg]). These data indicate that the loading conditions of the left ventricle predetermine the extent of global and segmental left ventricular dysfunction during the early phase of acute ischaemic injury.
Cardiovasc Res 1979 Mar
PMID:Afterload as a predeterminant of haemodynamics and segmental wall motion following coronary artery occlusion. 47 39

Ventricular conduction intervals between a stimulating pacemaker electrode at the right ventricular apex and an impulse detecting monophasic action potential electrode at the right ventricular septum were measured in nine subjects. The right ventricle was paced at a constant rate and programmed premature ventricular stimuli were introduced after every eighth paced beat beginning at the refractory period. The ventricular conduction intervals were measured from the pacemaker artefact to the onset of depolarisation of the MAP recording. In the control recordings a short period of prolonged (subnormal) conduction lasting for 5 to 26 ms after the refractory period was present in six of the nine subjects. In eight subjects a period of 'supernormal' conduction lasting from 50 to 180 ms was present. The effect of mexiletine was to increase the subnormal conduction and to abolish the supernormal conduction. It is concluded that a small degree of supernormal conduction occurs in the normal human ventricle possibly as a result of phase 4 depolarisation of cells of the specialised conducting system.
Cardiovasc Res 1979 Jun
PMID:Effect of mexiletine on conduction of premature ventricular beats in man: a study using monophasic action potential recordings from the right ventricle. 47 52

The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with dopaminergic activity, was evaluated during dosetitration and longterm infusion in 20 cardiosurgical patients with low cardiac output following coronary artery bypass grafting and/or valve replacement or repair. After infusion of four doses (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5). Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects (tachycardia and hypotension) were chiefly seen at higher doses (-->4 micrograms/kg/min). The beneficial haemodynamic effects were well maintained during the extended infusion period up to 36 hours at a mean dopexamine dose of 2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to the drug remained within the limits of clinical acceptability. During long-term infusion up to 36 hours there was no indication of tolerance or an effect attenuation. It can be concluded that dopexamine acting as "inodilator" with dopaminergic properties is an useful adjunct to the pharmacological spectrum in the management of low-output states following cardiac surgery.
Thorac Cardiovasc Surg 1992 Dec
PMID:The use of dopexamine after cardiac surgery: acute and long-term effects in patients with impaired cardiac function. 136 57

The acute hemodynamic and hormonal effects of incremental doses of a specific ovine renin inhibitor (RI: EMD 52 297) and captopril were compared in an ovine model of heart failure. Both RI and captopril inhibited the renin-angiotensin II (ANG II) system, although the decrease in plasma aldosterone (ALDO) was significant only during captopril infusion. Both agents exhibited strong vasodilator properties with similar decreases in mean arterial pressure (MAP, maximum decrease: RI = -20.5 +/- 2.2 mm Hg, p less than 0.001; captopril = -19.8 +/- 1.7 mm Hg, p less than 0.001) and left atrial pressure (LAP, maximum, decrease: RI = -6.8 +/- 1.5 mm Hg, p less than 0.01; captopril = -6.9 +/- 0.4 mm Hg, p less than 0.01) along with a slight increase in cardiac output (CO, maximum increase: RI = 0.54 +/- 0.11 L/min; captopril = 0.79 +/- 0.26 L/min). The slope of the response between MAP and LAP was similar in all animals, indicating that the agents have a similar effect on cardiac preload and afterload. The similar hemodynamic actions of RI and captopril in this model of congestive heart failure suggest that beneficial effects are due to inhibition of ANG II. Thus, orally active renin inhibitors may offer a useful therapeutic alternative when side effects preclude use of angiotensin-converting enzyme (ACE) inhibitors.
J Cardiovasc Pharmacol 1992 Feb
PMID:Comparison of the effect of renin inhibition and angiotensin-converting enzyme inhibition in ovine heart failure. 137 84

The effects of synthetic endothelin on the coronary circulation were studied in pentobarbital-anesthetized dogs and compared with those of Bay k 8644, a dihydropyridine calcium channel agonist, and U 46619, a thromboxane analogue. Intracoronary bolus administration of endothelin reduced coronary blood flow and increased coronary arterial resistance. Similarly, intracoronary bolus administration of equipotent doses of Bay k 8644 or U 46619 significantly reduced coronary blood flow and increased coronary arterial resistance. The coronary vasoconstrictor effects of endothelin were long-lasting as compared with the transient actions of Bay k 8644 and U 46619. Intracoronary bolus injection of endothelin also reduced left ventricular (LV) dP/dt arterial pressure (MAP), and cardiac output (CO). In contrast, Bay k 8644 increased LVdP/dt but did not alter CO or MAP. Intracoronary bolus injection of U 46619 did not affect MAP, CO, or LVdP/dt. In a separate group of animals, intracoronary infusion of nitrendipine significantly increased coronary blood flow and reduced coronary arterial resistance. Other cardiovascular parameters measured were not significantly altered. In the presence of nitrendipine, the effects of intracoronary administration of endothelin and U 46619 on coronary blood flow, coronary arterial resistance, and LVdP/dt were only partially antagonized. On the other hand, the effects of Bay k 8644 were completely prevented in the presence of nitrendipine. These studies show that at doses which reduce coronary blood flow to the same extent, only endothelin produces myocardial depression in anesthetized dogs. The cardiovascular actions of endothelin were only partially antagonized by nitrendipine, suggesting that mechanisms other than calcium influx through voltage-operated channels are involved.
J Cardiovasc Pharmacol 1992 Feb
PMID:Effects of intracoronary administration of endothelin in anesthetized dogs: comparison with Bay k 8644 and U 46619. 137 88

To test whether quinaprilat, a new angiotensin-converting enzyme (ACE) inhibitor, has any venous effect, we measured its immediate effects on mean circulatory filling pressure (MCFP), intravascular volume, and total body vascular (i.e., venous) compliance in conscious rats with healed myocardial infarction induced by coronary artery ligation. MCFP was determined by inflating a right atrial balloon to arrest the circulation instantly and temporarily. Total body vascular compliance was derived from total circulatory pressure-volume relationships as determined by series measurements of MCFP with different intravascular volume status. In 8 rats with mean infarct size of 26 +/- 4%, 30-min infusion of quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous pressures (MAP, CVP) by 8 and 0.7 mm Hg, respectively (p less than 0.02); heart rate (HR), MCFP, hematocrit, and blood volume remained unchanged. As compared with control vehicle infusion, quinaprilat increased total body vascular compliance (2.09 +/- 0.12 vs. 2.69 +/- 0.23 ml/kg/mm Hg; p less than 0.05) and decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs. 28.53 +/- 2.55 ml/kg; p less than 0.02). These data suggest that quinaprilat produces possible venodilation through improved total body vascular compliance, thereby reducing cardiac preload in this rat model of myocardial infarction.
J Cardiovasc Pharmacol 1992 Mar
PMID:Quinaprilat increases total body vascular compliance in rats with myocardial infarction. 137 25

Hemodynamic responses to intravenous (i.v.) injection of DPMA [N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl] adenosine); PD 125,944], a potent adenosine agonist with a 32-fold selectivity for the adenosine-2 (A2) receptor subtype, were characterized in conscious and anesthetized rats. In conscious rats instrumented with miniaturized pulsed-Doppler flow probes, i.v. injection of increasing doses of DPMA (3-30 micrograms/kg) had little effect on mean arterial pressure (MAP, maximal decrease -8 +/- 4 mm Hg) or renal and mesenteric resistance (maximal change 8 +/- 14 and 0 +/- 15%, respectively). In contrast, DPMA markedly reduced MAP (maximal decrease -61 +/- 8 mm Hg) in a dose-dependent (1-30 micrograms/kg) fashion in pentobarbital-anesthetized rats. The A2 agonist also caused a sustained, dose-dependent increase in heart rate (HR, maximal increase 75 +/- 12 beats/min) in conscious rats. The tachycardia and decrease in arterial pressure were completely reversed by i.v. administration of CGS 15943 (250 micrograms/kg), a selective adenosine receptor antagonist. Pretreatment with propranolol or hexamethonium significantly reduced but did not abolish the tachycardia, suggesting that the increase in HR was mediated only partially through reflex increases in sympathetic tone. These data indicate that (a) anesthesia potentiates the depressor actions of DPMA and (b) stimulation of A2 receptors increases HR through both direct and indirect mechanisms of action.
J Cardiovasc Pharmacol 1992 Mar
PMID:Selective adenosine-2 agonist produces both direct and reflex tachycardia in normotensive rats. 137 30

The regulation of vascular resistance, cardiac output, and thus blood pressure can be influenced by antihypertensive drugs acting at central and peripheral adrenergic receptors. The results presented here are from acute or chronic studies in 205 patients with mild or moderately severe essential hypertension: beta blockers (N = 101); alpha blockers (N = 36); a separate alpha- + beta-blocker combination or the combination agent labetalol (N = 37); prizidilol, a beta-blocker/vasodilator (N = 14); and dilevalol, a beta blocker/beta 2-stimulator (N = 17). Beta blockers without strong intrinsic sympathomimetic activity reduce heart rate and cardiac output immediately, but due to a reflex increase in total peripheral resistance index, blood pressure is unchanged or only slightly reduced. During chronic use, total peripheral resistance drops towards pretreatment level and pressure falls. Beta blockers with strong intrinsic sympathomimetic activity do not reduce heart rate or cardiac output at rest when sympathetic tone is low. During exercise, heart rate and cardiac output are reduced, but less than with conventional beta blockers, and resistance is unchanged or slightly reduced. An acute and chronic reduction in blood pressure can be produced by alpha-adrenergic receptor blockers (prazosin, doxazosin, trimazosin), and in these cases the fall occurs via a reduction in total peripheral resistance index without reflex tachycardia. These drugs tend to increase exercise stroke volume and cardiac output during chronic treatment. Free combinations of beta and alpha blockers or the use of the fixed combination drug, labetalol, induce marked reductions in blood pressure at rest and during exercise, mainly through a reduction in total peripheral resistance index. During chronic treatment, exercise stroke volume and cardiac output are well maintained. In acute studies with dilevalol, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were reduced (p less than 0.001) within 1 hour in 17 males with essential hypertension (WHO stage I) who received 200-400 mg oral dilevalol. The reduction in MAP was around 16-17% and was associated with an immediate fall in the total peripheral resistance index of the same magnitude (14%, p less than 0.001) after 1 hour at rest. There were no significant changes in heart rate or cardiac index.(ABSTRACT TRUNCATED AT 400 WORDS)
Cardiovasc Drugs Ther 1991 Jun
PMID:Acute and chronic hemodynamic effects of drugs with different actions on adrenergic receptors: a comparison between alpha blockers and different types of beta blockers with and without vasodilating effect. 167 63

Sixteen men with previously untreated diastolic blood pressure of 100-120 mm Hg were studied hemodynamically at rest supine and sitting and during a 100 W bicycle exercise. Blood pressure (BP) was recorded intra-arterially, and cardiac output (CO) by the dye-dilution method. After initial study, patients were treated with tiapamil in increasing doses (300-600 mg b.i.d., with a mean daily dose of 980 mg). The patients were restudied and then changed to felodipine (5-10 mg b.i.d., with a mean daily dose of 15 mg). Casual (cuff) BP at rest sitting was as follows: end placebo, 166/105 mm Hg; 1 year of tiapamil, 148/92 mm Hg; 1 year of felodipine, 139/86 mm Hg. Pretreatment hemodynamic results at rest sitting were as follows: BP, 169/105 mm Hg; MAP, 129 mm Hg; cardiac index (CI), 2.43 L/min/m2; total peripheral resistance index (TPRI), 4,305 dyn s/cm-5/m2. Both drugs reduced systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressure significantly in all situations. BP reduction seemed to be more pronounced on felodipine than on tiapamil. Felodipine reduced MAP by 15% at rest supine, 14% at rest sitting, and 11% during exercise. The BP reduction was entirely due to reduction in TPRI (15, 16, and 13%, respectively). CI as well as stroke index (SI) and heart rate (HR) were unchanged. Tiapamil did not reduce TPRI significantly and the fall in BP was due to a combination fall in TPRI and CI.
J Cardiovasc Pharmacol 1990
PMID:Chronic hemodynamic effects of tiapamil and felodipine in essential hypertension at rest and during exercise. 169 26

Peak III phosphodiesterase (PDE) inhibitors have combined positive inotropic and vasodilator effects. We studied 10 patients with chronic heart failure during and after infusion of intravenous (i.v.) ICI 153,110, an investigational peak III PDE inhibitor. Maximum hemodynamic response for the group occurred after cessation of infusion at a lower plasma drug concentration. At maximum hemodynamic response, cardiac index (CI) increased (2.4 +/- 0.5 vs. 3.2 +/- 0.37 L/min/m2, p less than 0.05) with a decrease in mean arterial pressure (MAP 91 +/- 5 vs. 80 +/- 3 mm Hg, p less than 0.05), pulmonary capillary wedge pressure (PCWP 25 +/- 2 vs. 17 +/- 3.1 mm Hg, p less than 0.01), systemic vascular resistance (SVR 1,422 +/- 106 vs. 983 +/- 97 dynes.s.cm-5, p less than 0.05) and pulmonary vascular resistance (PVR 227 +/- 39 vs. 16 +/- 31 dynes.s.cm-5, p less than 0.05). During the infusion, plasma renin activity (PRA) decreased from 6.34 +/- 2.53 to 3.6 +/- 3 ng/ml/h (NS). The five patients with high baseline PRA had a significant decrease (11.2 +/- 2.5 vs. 5.4 +/- 1.67 ng/ml/h, p less than 0.01) that preceded changes in CI and SVR by 1-2 h. These data suggest that reduction in PRA may have contributed to the hemodynamic effects of this peak III PDE inhibitor.
J Cardiovasc Pharmacol 1990 Sep
PMID:Acute neurohormonal and hemodynamic response to a new peak III phosphodiesterase inhibitor (ICI 153,110) in patients with chronic heart failure. 170 Feb 5


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