Temporary cardiointerval organization with varying degrees of acute normobaric hypoxia in a healthy person

The influence of acute normobaric hypoxia (ANH) on the male heart chronotropic effects was studied. Thus, a mild degree of ANH (14.5 % O2, 20 min), causing a decrease in blood oxygenation by 6.3 abs. %, accompanied by an initial (by 5 min) decrease in the RR and QT intervals. The average degree of ANH (12.3% O2) leads to a decrease in blood oxygenation by 19.7 abs. %. At the same time, in inverse relationship to the developing hypoxemia, RR and QT significantly decrease. Corrected values (Pc, PQc, QRSc, QTc) increase during the action period of an average degree of hypoxia, indicating an increase in the proportion of atrial contraction time, atrioventricular conduction of excitation and electrical ventricular systole in the total RR duration, which, apparently, provides optimal systolic heart effect. Key words: human, hypoxia, blood oxygenation, cardiointervals.

Maintained barostatic regulation of heart rate in digesting snakes (Boa constrictor)

When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enable snakes to maintain the cardiac limb for blood pressure regulation.

The dose-dependent effect of chronic Verapamil treatment on cardiac function in isolated rat heart with Hypertension

Funding Acknowledgements Type of funding sources: None. Introduction Verapamil, a calcium channel blocker, is used for treatment of hypertension, paroxysmal supraventricular tachycardia and angina pectoris. It primarily blocks L-type calcium channels preventing excessive influx of calcium into cardiomyocytes, leading to negative inotropic effect, and smooth muscle cells resulting in reduced relaxation of vasculature. With calcium antagonism it also causes negative chronotropic effect. However, there is no data on it’s dose-dependent effects on cardiac dynamic parameters and heart rate on isolated rat heart with hypertension. Purpose To investigate chronic, dose-dependent effects of Verapamil on cardiodynamic parameters in isolated rat heart with hypertension. Methods The present 4-week study was carried out on 24 spontaneously hypertensive Wistar Kyoto male rats (6 weeks old): Control (n = 6), rats treated with 0.5 mg/kg/day of Verapamil (n = 6), rats treated with 5 mg/kg/day of Verapamil (n = 6) and rats treated with 50 mg/kg/day of Verapamil (n = 6). Isolated rat hearts were perfused on Langendorff perfusion apparatus. Results Chronic, low-dose Verapamil treatment significantly depressed function of all cardiodynamic parameters of the hypertensive heart when compared to the rats treated with higher doses of Verapamil (p < 0.001), except on the coronary flow and heart rate when compared to the Control (p= 0.137; p = 1.000, respectively). There was no significant differences between Verapamil in middle dose (5 mg/kg/day) and the Control group in inotropic (p = 0.415) and lusitropic (p = 1.000) effects, while it significantly lowered values of coronary flow (p = 0.002). It achieved significantly lower inotropic, lusitropic and chronotropic effects (p < 0.001) than high Verapamil dose and significantly better inotropic (p = 0.017), lusitropic (p < 0.001), but not chronotropic effects than low-dose Verapamil treatment (p = 0.179). High-dose, chronic treatment with Verapamil significantly intensified function of the isolated rat heart with hypertension when compared to Control and lower doses of Verapamil (p < 0.001), without significant effects on coronary flow (p = 0.363). Conclusions Chronic treatment with Verapamil in high dose achieved better inotropic, chronotropic and lusitropic effects than treatment in low and middle doses of Verapamil, without significant effects on coronary flow. There is dose-depended effect of chronic Verapamil treatment on cardiac function of isolated rat heart with hypertension.

Amitriptyline functionally antagonizes cardiac H2 histamine receptors in transgenic mice and human atria

We have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H2R-TG) mice that overexpress the human H2 histamine receptor (H2R) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on H2Rs. Here, we wanted to determine whether the histamine effects in H2R-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from H2R-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM–10 μM) to higher concentrations (rightward shift) in left atrial preparations from H2R-TG. Similarly, in isolated perfused hearts from H2R-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the H2R-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from H2R-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at H2Rs in H2R-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline.

Cardiovascular Risk in Patients with Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders characterized by parathyroid hormone (PTH)-dependent hypercalcemia. Cardinal features include low trauma fractures, nephrolithiasis, and chronic kidney disease. Several experimental studies established that parathyroid hormone exerts actions on the cardiovascular (CV) system, including vasodilatation and positive inotropic and chronotropic effects. Observational studies, especially in severe cases, report a higher prevalence of hypertension, diabetes mellitus, lipid abnormalities, endothelial dysfunction, arrhythmias, and left ventricular hypertrophy in patients with PHPT, while the risk of CV events seems to be increased in severe cases. However, the effect of surgery is inconsistent on CV abnormalities and, more importantly, on CV disease (CVD) events, especially in mild cases. In the current review, we describe the available evidence linking PHPT and CVD, as well as the effect of surgical management and pharmacological treatment on CVD manifestations in patients with PHPT. Based on the current evidence, CVD is not considered an indication for surgery.