Inotropic drugs in the management of congestive heart failure.
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Biomedical subjects
Publications and source records attributed to C L Skelton.
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In isometrically contracting isolated cat papillary muscles, the mechanism determining the reduction in active tension (P) at lengths (L) below the optimal length (Lmax) for maximal tension development (Pmax) was studied. Increasing [Ca2+] from 1.25 to 5 mM, paired electrical stimulation and caffeine augmented P-O/max by 77,61 and 23% respectively, as well as the tension developed at any given length on the ascending limb of the length-active tension relation. To see whether below Lmax the degree of activation is dependent on length, these length-active tension relations were expressed as P/Pmax relative to L/Lmax where Pmax and Lmax in each inotropic state was 100%. These normalized length-active tension relations were not altered by different [Ca2+]o, but shifted upward and to the left by caffeine and paired stimulation. The effects of elevating [Ca2+] on the length-active tension relation suggests that restoring forces and fixed internal loads are not an important factor in decreasing active tension at short lengths. The effects of caffeine and paired stimulation support the view that in cardiac muscle inactivitation of contraction is a major factor determining the fall in active tension at decreasing length.
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The contractile properties of right ventricular papillary muscles from the hearts of 15 rats which had developed hypertension 6 weeks following renal artery ligation were compared with those from 14 normal litter-mates. In the experimental group, the heart weight-body weight ratio was increased by 39%, while the right ventricular weight-body weight ratio increased 20%. Right ventricular papillary muscles from the hypertensive rats demonstrated increased tension development at the apex of the length-active tension curve (P less than 0 X 0001), elevated maximal rate of tension development (P less than 0 X 001), and increased maximal velocity of contraction at muscle lengths corresponding to both a light preload and at Lmax (P less than 0 X 05). Resting tension and time-to-peak tension in the muscles from the hypertensive group were not significantly different from the normal group. Thus, improved right ventricular performance, in the presence of increased left ventricular afterload, may indicate the existence of a stimulus to increased function in hypertrophied muscle not yet negated by the adverse effects of direct exposure to stress.
The mechanism responsible for the enhancement of myocardial contractility in hyperthyroidism is unclear. The possibility that this mechanism may involve a direct effect on the contractile proteins was investigated using the glycerol-extracted muscle strip from right ventricular papillary muscles of euthyroid rabbits and rabbits made hyperthyroid by the intraperitoneal injection of 0.25 mg/kg 1-thyroxine for 10 d. Intact papillary muscles from the hyperthyroid rabbits had an enhanced rate of tension development, a decreased time to peak tension, and a slight though insignificant increase in active tension compared to control animals. Maximal isometric contractions were induced in glycerol-extracted cardiac muscle strips from the two animal groups by the addition of 5 mmol/litre ATP and 5 mmol/litre MgCl in a buffer solution containing 0.15 mol/litre Tris-HCl (pH 7.1) at 26 degrees C. Peak isometric tension was increased in glycerinated muscle strips from hyperthyroid rabbits (1.52+/-0.10 vs 1.26 +/-0.13g/mm2), but the differences did not reach statistical significance. However, there was a marked increase in the rate of tension development in the hyperthyroid group (62.5+/-5.4 vs 41.8+/-4.7 mg/mm-2/s, P less than 0.01). This increase in the rate of isometric tension development in both intact and glycerinated muscles from hyperthyroid rabbits may be related to changes in the intrinsic turnover of actomyosin cross-bridge links in this condition. Thus, these findings suggest that thyroid hormone may influence cardiac muscle function by a direct effect on the contractile proteins.
Induction of the diving reflex, by immersion of the face in cold water (2 degrees C) while the breath was held, converted paroxysmal atrial tachycardia to sinus rhythm within 15-35 seconds in seven patients (aged 22-66). Four had histories of heart attacks that had previously required vasopressor therapy, and two had been digitalised; three had no history of prior paroxysmal atrial tachycardia or heart-disease. The reported procedure, which is convenient, non-invasive, and can be self administered by the patient after brief instruction, may offer a useful adjunct to carotid-sinus massage and intravenous infusion of vasopressors for the treatment of paroxysmal atrial tachycardia.