PubMed Health⌕ Search

Biomedical subjects

J M Hartog

Publications and source records attributed to J M Hartog.

29 records · Page 2Linked to original sources
PubMed1986

Systemic and regional hemodynamic, antiarrhythmic and antiischemic effects of bevantolol in anesthetized pigs.

In doses of 0.5 to 3.0 mg/kg bevantolol caused dose-dependent decreases in cardiac output (10% to 35%), primarily due to negative chronotropic actions, as heart rate decreased by 10% to 25%. Stroke volume decreased after the highest dose (15%), due to a negative inotropic action (maximum left ventricular dP/dt decreased by 40%) and a mild vasoconstriction in systemic vascular beds. Decreases in perfusion of the heart, kidneys, liver, spleen, stomach, muscles and adrenals were similar to those in cardiac output. However, blood flow to the brain and small intestine was not significantly affected. Bevantolol (0.5 or 1.5 mg/kg IV) gave full protection against ventricular fibrillation during the first period (10 minutes) of proximal left anterior descending (LAD) coronary artery occlusion in the highest dose. After the third and last reperfusion period, 70% of these animals survived, while only 8% of the untreated and 15% of the animals treated with the lower dose survived. After permanent ligation of the LAD coronary artery at midpoint, bevantolol prevented ventricular fibrillation during the first phase of early ventricular arrhythmias but was unable to prevent it during the second phase of early arrhythmias. Administration of bevantolol (1.5 mg/kg) to animals in which the LAD coronary artery blood flow was reduced to 35% of baseline did not improve transmural myocardial blood flow to the ischemic zone. However, the drug caused a redistribution in favor of the endocardial layers. The changes in flow were accompanied by a narrowing of the arterial-coronary venous differences in pH and pCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties.

Intravenous infusions of 0.01-0.1 mg X kg-1 X min-1 of pimobendan, a benzimidazole-pyridazinone derivative in pigs with normal coronary circulation caused dose-dependent changes in heart rate (10-35%), left ventricular systolic pressure (-5 to -45%), left ventricular filling pressure (-20 to -40%) but had only a minor effect on the maximum rate of rise of left ventricular pressure (max LVdP/dt; 10-20%). The decrease in mean arterial blood pressure was primarily due to systemic vasodilation; peripheral resistance and cardiac output decreased by up to 40 and 14%, respectively. Vasodilation occurred in several vascular beds, but was particularly pronounced in the adrenals, stomach, small intestine and myocardium. Although the increase in myocardial blood flow favoured the epicardium, vascular conductance in both the endo- and epicardial layers was significantly increased. Myocardial O2 consumption (MVO2) was not affected despite the increase in heart rate. Bolus injections of 0.1-0.5 mg X kg-1 pimobendan produced similar changes in all haemodynamic variables, except max LVdP/dt which now increased by 30-70%. As in the infusion experiments, cardiac output tended to decrease due to a pronounced reduction in ventricular preload probably as a result of venodilation and the consequent reduction in cardiac filling. However, in animals where max LVdP/dt and cardiac output were reduced and pre- and/or after-load were increased by partial occlusion of the left anterior descending coronary artery, pimobendan clearly increased both max LVdP/dt and cardiac output. Pretreatment with propranolol did not modify any of the cardiovascular responses to pimobendan, thereby excluding the involvement of a beta-adrenoceptor mechanism. Pimobendan is thus a compound with vasodilator and positive inotropic properties that improves cardiac output in animals with severe myocardial ischaemia. The finding that the mild tachycardia caused by pimobendan was not accompanied by an increase in MVO2 warrants investigation to evaluate its usefulness in the treatment of heart failure.

Adrenergic beta-Antagonists↗
PubMed1986

Alleviation of myocardial ischaemia after administration of the cardioselective beta adrenoceptor antagonist bevantolol.

A 15 min reduction in blood flow in the left anterior descending coronary artery to 35% of baseline in open chest anaesthetised pigs produced a 25% decrease in cardiac output and a similar fall in maximum left ventricular dP/dt, whereas left ventricular filling pressure increased from 10(1) to 14(1) mmHg. The decrease in perfusion of the myocardial area nourished by the left anterior descending coronary artery was not evenly distributed since the endocardial to epicardial flow ratio decreased from 0.93(0.07) to 0.48(0.06). Regional myocardial wall thickening of the ischaemic segment decreased from 0.36(0.03) to 0.14(0.03), whereas the arterial-coronary venous differences in pH and PCO2 tripled. Subsequently, eight animals received 1.5 mg X kg-1 of the cardioselective beta adrenoceptor antagonist bevantolol, whereas seven other animals were treated with the solvent. In the following 15 min the cardiovascular performance of the solvent treated animals did not change appreciably, although there was a tendency to further deterioration. Bevantolol did not improve transmural myocardial blood flow to the ischaemic zone but caused a redistribution in favour of the endocardial layers since the endocardial to epicardial flow ratio almost returned to baseline. These changes in flow were accompanied by a narrowing of the arterial-coronary venous differences in pH and PCO2, but regional myocardial function did not improve. In another series of experiments, however, bevantolol (1.5 mg X kg-1) decreased the velocity of regional wall thickening of normal myocardium by 22(2)% as a result of its negative inotropic properties. Thus bevantolol appears to alleviate ischaemia, and the increase in diastolic perfusion time (17%) may be one of the major mechanisms.

Adrenergic beta-Antagonists↗
PubMed1986

Inotropic and vasodilating properties of amrinone depend on the mode of administration.

Intravenous infusion of amrinone at increasing rates (10-100 micrograms kg-1 min-1, N = 8) caused dose dependent decreases in left ventricular filling pressure (up to 22%, P less than 0.05) and cardiac output (up to 16%, P less than 0.05), but had no effect on heart rate, max LVdP/dt or total systemic vascular resistance in anaesthetized open-chest pigs. Despite unchanged total systemic vascular resistance, tissue vascular resistance decreased significantly in the heart, stomach, adrenals and kidneys. Although transmural left ventricular perfusion was not influenced by amrinone, coronary blood flow was redistributed in favour of the epicardium, as endo-epi blood flow ratio decreased from 0.95 +/- 0.03 to 0.82 +/- 0.03 (P less than 0.05). In the same model an intravenous bolus of 1 mg kg-1, followed by a continuous infusion of 50 micrograms kg-1 min-1 (N = 8), caused immediate changes (P less than 0.05) in left ventricular filling pressure (-35%), max LVdP/dt (+55%), heart rate (+15%) and total systemic vascular resistance (-15%). The changes in filling pressure and systemic vascular resistance persisted during the next 25 minutes, but maxLVdP/dt returned gradually to baseline in spite of increasing plasma concentrations of the drug. In the conscious pig (N = 4), administration of a 1 mg kg-1 bolus in the pulmonary artery led to similar increases in heart rate (15%) and max LVdP/dt (26%), while systolic left ventricular pressure was not affected. Direct infusion into the left anterior descending coronary artery (10-40 micrograms kg-1 min-1, N = 5) had negligible effects on overall haemodynamics and regional myocardial function. The only significant changes were a vasodilation in the coronary vascular bed accompanied by dose dependent increases in the coronary venous O2-content. From our study it appears that a bolus injection, as given in the clinical setting, is required to elicit an increase in max LVdP/dt and arterial vasodilation but that the effect on left ventricular preload is not sensitive to different modes of administration.

Amrinone↗
PubMed1986

The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital-anaesthetized pigs with or without beta-adrenoceptor blockade.

The effects of the 1,4-dihydropyridine derivative nisoldipine, infused intravenously (i.v.) at 3 different rates (0.25, 0.5 and 1.0 microgram kg-1 min-1), were studied in anaesthetized pigs on cardiovascular performance with or without beta-adrenoceptor blockade produced by propranolol. Nisoldipine caused dose-dependent decreases in arterial blood pressure (30%), systemic vascular resistance (30%) and left ventricular filling pressure (15%), but raised heart rate (25%) and LV dP/dt max (20%). Cardiac output was not significantly affected. Transmural myocardial blood flow and vascular conductances increased dose-dependently after nisoldipine. The elevation in blood flow to the left ventricle favoured epicardial layers. Endocardial blood flow showed small increases as the changes in conductance of the endocardial layer more than compensated for the loss in perfusion pressure. The endo-epi blood flow ratio decreased from 1.16 +/- 0.05 to 0.70 +/- 0.01. Myocardial O2-consumption was unaltered as the decrease in arterial-coronary venous O2-content difference (30%) was balanced by the increase in transmural blood flow. Nisoldipine increased blood flow to skeletal muscle (500%), stomach (50%) and adrenals (25%), but decreased that to the liver (50%), spleen (25%) and kidneys (25%). No changes were noticed in the small intestine, skin and brain. In spite of differential effects on blood flow, vascular conductance in all organs and tissues, with the exception of the liver, increased. After beta-adrenoceptor blockade the responses of mean arterial blood pressure, cardiac output and systemic vascular resistance to nisoldipine remained virtually unchanged, but the elevations in heart rate and LV dP/dt max were abolished, as was the decrease in left ventricular filling pressure. A higher dose of nisoldipine was required after beta-adrenoceptor blockade to elicit significant vasodilatation in the epi- and endocardial layers. However, the reduction in endo-epi blood flow ratio by nisoldipine was not affected by propranolol. Myocardial O2-consumption tended to decrease as the diminution in the arterial-coronary venous O2-content difference (30%) slightly exceeded the increase of left ventricular blood flow (30%). Except for the brain and liver, effects of nisoldipine on regional vascular conductances were attenuated after beta-adrenoceptor blockade.

Adrenergic beta-Antagonists↗
PubMed1986

Usefulness of pimobendan in the treatment of heart failure.

The effects of the benzimidazole-pyridazinone pimobendan (UD-CG 115 BS) on systemic haemodynamics, myocardial performance and the distribution of cardiac output were studied in open-chest anaesthetized pigs. After intravenous bolus injections (0.1-0.5 mg X kg-1, n = 7) increases in heart rate (up to 37%), LVdP/dtmax (up to 54%) and decreases in systemic vascular resistance (up to 33%) and left ventricular filling pressure (up to 50%) were observed, while cardiac output was unchanged. Vasodilation occurred in nearly all regional vascular beds, but was most pronounced in the adrenals (200%), followed by stomach (150%), small intestines (130%), heart (125%) and brain (110%). O2-consumption was not affected in spite of the increases in heart rate and myocardial inotropy. To evaluate the direct effects on the myocardial, pimobendan was also infused (1-5 micrograms X kg-1 X min-1, n = 7) directly into the left anterior descending coronary artery. In addition to a marked vasodilation of the coronary bed (140%), also a lowering of the left ventricular filling pressure (up to 20%) and cardiac output (15%) was observed, but no changes in regional myocardial function, LVdP/dtmax and systemic vascular resistance occurred. Immediately after intracoronary bolus injections (1 mg X kg-1, n = 4), vasodilation of the coronary vessels was apparent, but myocardial contractility was not affected. This may explain that cyclic AMP content, determined in biopsies excised 30 s after injection, was unaltered. It may be concluded that pimobendan exerts actions on the cardiovascular system which may be useful in the treatment of heart failure.

Animals↗
PubMedDate not supplied

The influence of fish oil diet and norepinephrine treatment on fatty acid composition of rat heart phospholipids and the positional fatty acid distribution in phosphatidylethanolamine.

The effect of chronic norepinephrine (NE) administration with increasing dosage from 1-4 mg/kg over a period of 2 weeks was studied on cardiac phospholipids and their fatty acid distribution in rats. Animals were fed a control diet or a 10% cod liver oil (CLO)-enriched diet. The relative distribution of various polyunsaturated fatty acids esterified to the 1- and 2-position of the phosphatidylethanolamine fraction was estimated. NE stress during control feeding significantly reduced the total phospholipid content in rat heart. No differences in the phospholipid class distribution were found. However, CLO feeding as well as chronic NE administration resulted in a decrease of omega 6 fatty acids, mainly C 18:2 omega 6 and C 20:4 omega 6, which was compensated with an increase in omega 3 fatty acids, mainly C 20:5 omega 3 and C 22:6 omega 3. The changes in fatty acid composition qualitatively agree with those reported by Gudbjarnason et al. (23), except that the mortality in our NE-treated control or CLO-fed groups was considerably lower. It can probably be attributed to a different mode of NE administration. On the other hand, at the end of the CLO feeding period in rats treated with NE or not, comparing with control fed rats without NE treatment, the incidence rate of ST segment elevation in electrocardiogram (ECG) recorded under light diethylether-induced anesthesia was higher. Independent of whether the fatty acid composition of myocardial phospholipids was dietary or pharmacologically manipulated, most of the polyunsaturated fatty acids were found at the 2-position of the phosphatidylethanolamine molecules. The polyunsaturated fatty acids account for 45-50% of the fatty acyl residues and preferentially occupy the 2-position, where they can exchange for each other.

Animals↗
PubMedDate not supplied

Intracoronary infusion of small doses of nifedipine lowers regional myocardial O2-consumption without altering regional myocardial function.

Intracoronary infusion of low doses (0.1-0.3 microgram X kg-1) of nifedipine caused dose-dependent decreases in regional myocardial O2-consumption, without significant changes in any of its major global hemodynamic determinants: heart rate, left ventricular systolic and end-diastolic pressure and maxLVdP/dt. Furthermore, regional myocardial function was unaltered. It is suggested that nifedipine decreased myocardial O2-consumption by a direct effect on myocardial metabolism. Some of the possible mechanisms involved are discussed.

Animals↗
PubMedDate not supplied

The effects of dietary mackerel oil on plasma and cell membrane lipids, on hemodynamics and cardiac arrhythmias during recurrent acute ischemia in the pig.

Fish-oil nutrition leads to a change in fatty acid composition of cellular membranes. To investigate whether this affects cardiac responses to acute myocardial ischemia, pigs were fed a 9.1% (w/w) mackerel-oil (n = 8) or 9.1% (w/w) lard-fat diet (n = 8). Eight weeks mackerel-oil feeding reduced plasmacholesterol (51%) and triglyceride (48%), while the n-6 fatty acids of cardiac and platelet membrane phospholipids were partially replaced by n-3 fatty acids. After 8 weeks the animals were anesthetized and the left anterior descending coronary artery was occluded 6 times for a period of 5 min at 15 min intervals. Recovery of cardiac function and the incidence of cardiac arrhythmias were similar for both dietary groups. However, during the last reperfusions, hyperemic responses were less in magnitude and shorter lasting in the lard-fat (81 +/- 17 ml/min) than in the mackerel-oil group (129 +/- 18 ml/min). This may be caused by a difference in thromboxane synthesis, as coronary venous blood thromboxane B2 levels were higher in the lard-fat (77 +/- 6 pg/ml) than in the mackerel-oil group (19 +/- 7 pg/ml, P less than 0.05) during peak hyperemia. The low baseline levels of both thromboxane B2 and 6-keto prostaglandin F1alpha in fish-oil fed animals originate from the reduced content of precursor fatty acid in the membrane phospholipids. In conclusion, despite marked changes in membrane fatty acid composition induced by prolonged feeding with fish oil, no modification of recovery of cardiac function and of incidence of cardiac arrhythmias was found during acute recurrent ischemia.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Cardiovascular actions of amrinone in anesthetized open-chest pigs with an acute mild stenosis in the left anterior descending coronary artery.

A 15 minute reduction of the flow in the left anterior descending coronary artery (LAD) to 50% of baseline caused a 10% decrease in cardiac output in anesthetized open-chest pigs (n = 12), together with a fall in max LV dP/dt (20%), mean arterial blood pressure (15%) and stroke volume (7%), while left ventricular filling pressure rose from 9 +/- 1 to 15 +/- 1 mmHg. The decrease in perfusion of the LAD nourished myocardium was not evenly distributed as endo-epi blood flow ratio decreased from 1.03 +/- 0.05 to 0.50 +/- 0.08. Regional myocardial wall thickening of the ischemic segment decreased from 34 +/- 6 to 7 +/- 3%, while the arterio-coronary venous differences in pH and PCO2 increased five and two fold, respectively. Subsequently, 6 animals received 1 mg X kg-1 plus 50 micrograms X kg-1 X min-1 amrinone for 10 minutes, whereas 6 other animals were treated with saline. In the following 10 minutes cardiovascular performance in the saline-treated animals did not change dramatically, although there was a tendency to further deterioration. Administration of amrinone led to a decrease in left ventricular filling pressure (30%), stroke volume (20%), cardiac output (10%) and mean arterial pressure (20%). There was also a mild positive chronotropic action (15%) and an initial positive inotropic action as indicated by an increase in max LV dP/dt (25%). The positive inotropic effect, however, was short-lasting as max LV dP/dt returned to baseline within 10 minutes after the bolus injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗