Isometric Contractile Tension Research Articles

Expression of Melatonin Receptor 1 in Rat Mesenteric Artery and Perivascular Adipose Tissue and Vasoactive Action of Melatonin

Melatonin is released by the pineal gland and can modulate cardiovascular system function via the G protein-coupled melatonin receptors MT1 and MT2. Most vessels are surrounded by perivascular adipose tissue (PVAT), which affects their contractility. The aim of our study was to evaluate mRNA and protein expression of MT1 and MT2 in the mesenteric artery (MA) and associated PVAT of male rats by RT-PCR and Western blot. Receptor localization was further studied by immunofluorescence microscopy. Effects of melatonin on neurogenic contractions were explored in isolated superior MA ex vivo by measurement of isometric contractile tension. MT1, but not MT2, was present in MA, and MT1 was localized mainly in vascular smooth muscle. Moreover, we proved the presence of MT1, but not MT2 receptors, in MA-associated PVAT. In isolated superior MA with intact PVAT, neuro-adrenergic contractile responses were significantly smaller when compared to arteries with removed PVAT. Pre-treatment with melatonin of PVAT-stripped arterial rings enhanced neurogenic contractions, while the potentiating effect of melatonin was not detected in preparations with preserved PVAT. We hypothesize that melatonin can stimulate the release of PVAT-derived relaxing factor(s) via MT1, which can override the direct pro-contractile effect of melatonin on vascular smooth muscle. Our results suggest that melatonin is involved in the control of vascular tone in a complex way, which is vessel specific and can reflect a sum of action on different layers of the vessel wall and surrounding PVAT.

Sarcomere length-tension relationship in failing human myocardium

The Starling relationship is a fundamental component of cardiac muscle physiology. Although many researchers have studied the length-tension relationship in human myocardium, none have done it at the sarcomere level. The present study examined the effects of sarcomere length (SL) on contractile parameters in cardiac trabeculae from ischemic and non-ischemic failing human hearts, as well as those mechanically unloaded by a left ventricular assist device (LVAD).Methods:Using laser diffraction techniques, resting SLs were measured in right ventricular cardiac trabeculae (n 10: Average dimensions (mm): 0.33 0.05 Width, 0.19 0.01 Thickness, 2.94 0.32 Length) from failing human hearts. As muscle length was incremented in a stepwise manner (25.0 um/step), resting SL and isometric contractile tension were assessed. Based on the SL-tension relationship, we determined the SLs that produced a developed tension of 20, 50, and 80% of maximal developed tension (Tmax) for each trabeculae. Results: For all groups, developed tension, rate of maximal tension rise, and rate of maximal tension decline all increased linearly as SL was increased. Diastolic tension increased minimally between SLs of 1.7 um to 2.0 um, and in some cases at SLs beyond 2.0 um, it increased in a nonlinear fashion. The SL associated with a particular percent of Tmax was remarkably consistent across all trabeculae: 1.92 0.02 um 20%(Tmax-To); 2.09 0.02 um 50%(Tmax-To); and 2.25 ± 0.01 um 80%(Tmax-To); (To represents the minimal developed tension). These relationships did not seem to be affected by etiology or prior LVAD support. Conclusion: SL can be reliably measured in very thin cardiac trabeculae from human hearts. Although the shapes of the active SL-tension relationships are quite similar, there is substantial heterogeneity in the shapes of the passive SL-tension relationships. Our study also shows that Tmax, often used as a starting point during in vitro analysis, is achieved at non-physiological SLs ( 2.35 um). Therefore, in studies where SL cannot be measured, using a percent of the tension between Tmax and To one can reliably set the preload at a more physiologic SL.

Exercise training alters aortic vascular reactivity in hypothyroid rats.

Hypothyroidism induces a number of cardiovascular adaptations in rats, including decreases in blood flow to high-oxidative skeletal muscle and increases in total peripheral resistance. Conversely, exercise training results in elevations in blood flow to high-oxidative skeletal muscle and decreases in vascular resistance. The purpose of this study was to determine whether hypothyroidism induces changes in the vasomotor responses of arterial vessels and whether exercise training modifies these responses. Rats were divided into three groups, sedentary euthyroid (S-Eut), sedentary hypothyroid (S-Hypo), and exercise-trained hypothyroid (ET-Hypo). Responses to vasoactive compounds were examined in vitro using abdominal aortic rings. Maximal isometric contractile tension (g/mm2) evoked by KCl and norepinephrine (NE) were not different among groups. However, sensitivity to KCl [agonist concentration producing 50% of maximal vasoconstrictor response (EC50; in mM): S-Eut, 21.1 +/- 1.1; S-Hypo, 35.7 +/- 2.7; ET-Hypo, 43.8 +/- 2.0] and to NE [EC50 (in M): S-Eut, 4.0 x 10(-8) +/- 2.3 x 10(-8); S-Hypo, 8.3 x 10(-8) +/- 3.4 x 10(-8); ET-Hypo, 3.6 x 10(-7) +/- 1.1 x 10(-7)] was different among groups, and in the order S-Eut > S-Hypo > ET-Hypo. Maximal vasodilator responses induced by acetylcholine (10(-7) M NE preconstriction) were lower in rings from S-Hypo animals than those from S-Eut and ET-Hypo rats. Dilatory responses induced by sodium nitroprusside (SNP) with the same NE preconstriction were not different among groups. However, with a 10(-4) M NE preconstriction, maximal dilatory responses induced by SNP were lower in vessels from hypothyroid animals. Dilatory responses to forskolin (10(-4) M NE preconstriction) were not different among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasoconstrictor properties of rat aorta are diminished by hindlimb unweighting.

Prolonged bed rest and exposure to weightlessness in humans result in cardiovascular alterations that are characterized by orthostatic intolerance and decreased exercise capacity. Modifications of cardiovascular function have been suggested to be causally related to changes in peripheral vascular reactivity. Rat hindlimb unweighting (HU) was used as an animal model to determine whether prolonged decreases in weight-bearing activity induce changes in vasoreactivity of peripheral arterial vessels. Responses to vasoactive compounds were examined in vitro using isolated abdominal and thoracic aortic rings. Maximal isometric contractile tension evoked by the vasoconstrictors KCl (10-100 mM), norepinephrine (NE; 10(-9)-10(-4) M), phenylephrine (10(-9)-10(-4) M), arginine vasopressin (10(-13)-3 x 10(-5) M), and CaCl2 (10(-6)-10(-2) M) was lower in abdominal aortic rings from HU rats. Sensitivity [agonist concentration that produced 50% of maximal vasoconstrictor response (EC50)] to KCl was enhanced in segments from HU animals but was not different for the other constrictors. Maximal contractile responses of thoracic aortic rings to KCl (10-100 mM) and NE (10(-9)-10(-4) M) were also attenuated by HU. In abdominal aortic rings preconstricted with 10(-4) M NE, maximal vasodilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and 8-bromoguanosine 3',5'-cyclic monophosphate (10(-6)-10(-2) M) were greater in vessel rings from HU rats. However, with 10(-7) M NE preconstriction, maximal dilatory responses induced by sodium nitroprusside (10(-10)-10(-4) M) and acetylcholine (10(-9)-10(-4) M) were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta.

We tested the hypothesis that adaptations in peripheral arterial vasoreactivity are induced by exercise training. Male rats were trained to run on a treadmill at 30 m/min (15 degrees incline) for 1 h/day 5 days/wk for 10-12 wk. Efficacy was indicated by a 51% increase (P < 0.05) in citrate synthase activity in soleus muscle of exercise-trained (ET) rats compared with that of sedentary (SED) control rats. Responses to vasoactive compounds were examined in vitro using rings of abdominal aorta. Maximal isometric contractile tension evoked by KCl, norepinephrine (NE), and phenylephrine were not different between groups; sensitivity to phenylephrine was also not different between groups. However, sensitivity was lower for both KCl and NE in vessels from ET animals. Endothelium removal did not influence KCl sensitivity but did abolish the difference in NE sensitivity of vessel segments between ET and SED animals. Maximal vasodilator responses induced by acetylcholine (ACh; NE or prostaglandin F2 alpha preconstriction) were greater in vessel rings from ET rats. However, dilatory responses by sodium nitroprusside (NE or prostaglandin F2 alpha preconstriction) and forskolin (NE preconstriction) were not different between groups, indicating that the augmented ACh-induced dilatory response resulted from an adaptation of the endothelium. Blockade of nitric oxide synthase activity diminished ACh-induced vasodilation by 79 and 100% in SED and ET rats, respectively. These results indicate that training alters vasomotor function in rat abdominal aortas through adaptations of both endothelium and smooth muscle.

PH-induced effects on median frequency and conduction velocity of the myoelectric signal

H+ accumulation at the sarcolemma is believed to play a key role in determining the electrophysiological correlates of fatigue. This paper describes an in vitro method to externally manipulate muscle pH while measuring the resultant effect on surface-detected median frequency (MDF) and conduction velocity (CV) parameters. Hamster muscle diaphragm strips (n = 8) were isolated with the phrenic nerve intact and placed in an oxygenated Krebs bath (26 degrees C). The muscle was clamped to a noncompliant load cell to measure isometric contractile tension. Tetanic contraction was developed via 40-Hz supermaximal stimulation of the phrenic nerve. Differential signals were recorded from three electromyogram (EMG) detection surfaces for computation of CV (via the phase shift in the EMG signals) and MDF. Repeated trials were conducted at bath pHs of 7.4, 7.0, and 6.6. Bath pH was altered by aerating predetermined concentrations of O2 and CO2 into the bath. Decreases in bath pH resulted in decreases in both initial MDF and initial CV. The differences in initial MDF and initial CV were significant (P less than 0.001) for each of the bath pH conditions. In general, the change in bath pH resulted in an equal percent change in initial MDF and initial CV. This suggests that the change in bath pH caused a decrease in CV without significantly altering the fundamental shape of the M wave. In contrast, the EMG was altered differently during stimulated contractions. During stimulation, the rate of decay of CV was 65% of the rate of decay of MDF.(ABSTRACT TRUNCATED AT 250 WORDS)

Inotropic and Chronotropic Profile of MCI-154: Comparison with Isoproterenol and Imazodan in Guinea Pig Cardiac Preparations

Although recent studies indicate that MCI-154 exerts novel positive inotropic actions in heart muscle, the chronotropic properties of this new drug remain undefined. The present study compared the inotropic/chronotropic profile of MCI-154 with those of a nonselective beta 1/beta 2-agonist (isoproterenol, Iso) and a type III phosphodiesterase inhibitor (imazodan, CI-914) in cardiac preparations isolated from guinea pigs. The inotropic efficacy of MCI-154 was approximately equal to that of Iso and CI-194 in electrically paced (1 Hz) atrial muscle, with each agent increasing isometric contractile tension approximately 170% above basal (predrug) values. The inotropic EC50 for Iso (2.9 +/- 0.7 x 10(-9) M) was several orders of magnitude less than that for MCI-154 (1.4 +/- 0.4 x 10(-4) M) and CI-914 (1.1 +/- 0.2 x 10(-4) M). The inotropic potency of MCI-154 was equivalent in atrial and left ventricular myocardium. Both Iso and CI-194 substantially increased spontaneous beating frequency of sinoatrial preparations, and the inotropic/chronotropic potency ratio for each was unity. In contrast, MCI-154 exerted a slight negative chronotropic action on basal sinoatrial rate. Moreover, the negative chronotropic influence of MCI-154 was increased several-fold in the presence of Iso-stimulated maximal increases in heart rate (HR), and this inhibitory chronotropic action of MCI-154 was not prevented by muscarinic receptor blockade with atropine. These findings indicate that MCI-154 has a unique inotropic/chronotropic profile in cardiac tissues of guinea pigs in that this drug (a) efficaciously increased myocardial contractility, (b) had minimal effect on basal sinoatrial automaticity and yet (c) markedly inhibited sympathetically mediated sinus tachycardia.

Does acute exposure to amiodarone prolong cardiac action potential duration?

1. 1. The acute effects of a potent antiarrhythmic agent, amiodarone (AM), were studied in isolated guinea pig ventricular muscle. Transmembrane action potentials were recorded by conventional microelectrode techniques, and isometric contractile tension, by a strain gauge. 2. 2. Short-term (30 min) exposure to 4.4 × 10 −5 M AM did not significantly effect action potential characteristics, whereas the peak developed tension was significantly depressed. 3. 3. On the other hand, long-term (3–5 hr) exposure to the same concentration of AM led to a significant decrease in the resting membrane potential, amplitude of action potential, overshoot of action potential, maximum upstroke velocity of action potential, and the peak developed tention. However, the duration of action potential at all levels of repolarization was not significantly effected by 4.4 × 10 −5 M AM during the entire duration of the experiment. 4. 4. These results suggest that the acute AM's antiarrhythmic actions reported may be not due to APD-lengthening action, but probably due to other actions (mainly, inhibition of Na + channels, Ca 2+ channels).

Specific Effects of Nitroprusside on Myocardial O2 Balance Following Coronary Ligation in the Dog Heart

The effect of gradual infusion of nitroprusside was studied in healthy and in ischemic hearts. In two areas of the left ventricular surface (ischemic and non-ischemic) local coronary blood flow was measured by a thermistor technique. Isometric contractile tension was recorded with strain gauge arches, and nicotinamide-adenine-dinucleotide (NADH) redox state was measured simultaneously in both regions using a two-channel fluorometer. Aortic blood pressure was also recorded. It was found that at an infusion rate of 1.0 microgram/kg/min, nitroprusside increased regional coronary blood supply in the healthy heart as well as in the ischemic and nonischemic areas of left anterior descending artery (LAD)-ligated hearts. Flow elevation was similar in all regions (37.0 +/- 6.1, 42.5 +/- 13.5 and 45.36 +/- 14.8%, respectively). At higher doses, a decrease of 6-10% in blood pressure had a detrimental effect on the coronary flow to the ischemic region without reducing flow to the nonischemic region. The NADH redox level was not significantly improved by nitroprusside in spite of elevated coronary blood supply to all regions examined. Moreover, higher doses of nitroprusside resulted in a significant elevation in NADH levels that could be correlated to the decrease in blood pressure. It is concluded that the effect of nitroprusside on coronary blood supply and myocardial O2 balance may be strongly dependent on the magnitude of its effect on blood pressure.

Differential effects of L-propionylcarnitine on the electrical and mechanical properties of guinea pig ventricular muscle in normal and acidic conditions

We studied the effects of L-propionylcarnitine (PC) on transmembrane action potentials and isometric contractile tension in isolated guinea pig ventricular papillary muscles. The effects of 5 concentrations of PC (10(-5), 10(-4), 10(-3), 10(-2) and 3 X 10(-2)M) were examined in both normal (pH 7.4) and acidic (pH 6.9) conditions. The concentrations of 10(-5) to 10(-2)M had no significant effect on action potential amplitude, maximum upstroke velocity of phase 0 and resting potential, in either condition. At pH 7.4, action potential duration (ADP) was significantly (P less than 0.05) or insignificantly shortened by the drug depending upon the concentration used. At pH 6.9, however, the APD was prolonged by moderate PC concentrations (10(-3) and 10(-2)M), in which the effective refractory period (ERP) was also lengthened, associated with an increased ERP/APD ratio. In both pH conditions, the highest concentration (3 X 10(-2)M) significantly (P less than 0.05) decreased all these action potential parameters. PC had a biphasic effect on the developed tension. In both pH conditions, low PC concentrations (10(-5) to 10(-3)M) produced an initial augmentation of the contraction, followed by subsequent reduction. The initial augmentation disappeared by pretreatment with reserpine or propranolol, suggesting the involvement of beta-adrenoceptors. In the steady state, all PC concentrations produced a negative inotropic effect at pH 7.4, while at pH 6.9 only high concentrations (10(-2)M and 3 X 10(-2)M) had this effect. These results suggest that the effects of PC in an acidic condition differ considerably from those in a normal pH condition and that limited concentrations of PC (10(-3) to 10(-2)M) may prevent re-entrant arrhythmias from developing under acidic conditions via lengthening of the ERP, without deleterious effects on the contractile force.

Increased sensitivity of the isometric contraction of the neonatal isolated rat atria to halothane, isoflurane, and enflurane.

Isolated atria from neonatal (0-5 day old) and adult (50 +/- 5 day old) rats were perifused in oxygenated Kreb's Henseleit solution at 30 +/- 0.5 degrees C and exposed to four different concentrations of halothane, isoflurane, or enflurane while isometric contractile tension was recorded and compared with control atria. ED50 values (mM of anesthetic required to produce 50% reduction in contractile tension) of neonates for halothane (0.18 +/- 0.01), isoflurane (0.41 +/- 0.05), and enflurane (0.41 +/- 0.04) were significantly lower than those of adults (0.35 +/- 0.02, 0.80 +/- 0.05, and 1.15 +/- 0.05, respectively). Furthermore, neonatal ED50 calculated as per cent of adult ED50 was significantly less for enflurane (35%) than for halothane (54%) or isoflurane (51%).

Evidence That Halothane Inhibits Norephinephrine Release from Sympathetic Nerve Endings in Dog Saphenous Vein by Stimulation of Presynaptic Inhibitory Muscarinic Receptors

Studies were done to determine the mechanism whereby halothane inhibits the release of norepinephrine from postganglionic sympathetic nerve endings. Helical strips of dog saphenous vein were mounted for superfusion and measurement of isometric contractile tension in the presence or absence of halothane (1.2 or 2.5%). Endogenous norepinephrine overflowing in response to electrical stimulation (10 V, 2 Hz for 15 min), and the content of norepinephrine remaining in the veins after stimulation, were measured by liquid chromatography with electrochemical detection. The data indicate that halothane decreased the stimulation-evoked release of norepinephrine by stimulation of prejunctional inhibitory muscarinic receptors. Evidence was also obtained that halothane may impair clearance of norepinephrine from the synaptic cleft.

Evidence that Halothane Inhibits Norepinephrine Release from Sympathetic Nerve Endings in Dog Saphenous Vein by Stimulation of Presynaptic Inhibitory Muscarinic Receptors

Studies were done to determine the mechanism whereby halothane inhibits the release of norepinephrine from postganglionic sympathetic nerve endings. Helical strips of dog saphenous vein were mounted for superfusion and measurement of isometric contractile tension in the presence or absence of halothane (1.2 or 2.5%). Endogenous norepinephrine overflowing in response to electrical stimulation (10 V, 2 Hz for 15 min), and the content of norepinephrine remaining in the veins after stimulation, were measured by liquid chromatography with electrochemical detection. The data indicate that halothane decreased the stimulation-evoked release of norepinephrine by stimulation of prejunctional inhibitory muscarinic receptors. Evidence was also obtained that halothane may impair clearance of norepinephrine from the synaptic cleft.

Contractile dysfunction of atrial myocardium from endotoxin-shocked guinea pigs.

Atrial muscle isolated from guinea pigs subjected to Escherichia coli endotoxin shock was used to study the myocardial changes associated with this experimental disease state. Isometric contractile tension and its first derivative (dT/dt) consistently were depressed by about 45% in muscle from the shock group (P less than 0.001), but contraction time intervals of the shock tissues were not significantly altered. The inotropic deficit of shock was completely antagonized by high concentrations of Ca2+ (greater than 4.5 mM). However, the maximal positive inotropic response to increased frequency of stimulation (0.1-2.2 Hz) only partially antagonized shock-induced cardiac depression. Heart muscle from shocked animals exhibited increased sensitivity to the negative inotropic effects of Mn2+, low Ca2+, and gentamicin; recovery from the depressant actions of these agents was prolonged 3.6- to 4.8-fold in shock. However, the negative inotropic potency of slow Ca2+ channel blockers, D 600 and nifedipine, was unaffected by shock. Similarly, studies with an isoproterenol-activated slow Ca2+ channel technique demonstrated equivalent inotropic responses of shock and control heart muscle. Present data provide evidence for a disruption of myocardial Ca2+ metabolism associated with endotoxin-induced inotropic depression of the heart but suggest that slow Ca2+ channels of the sarcolemma remain functional in this disease state.

Glucocorticoid enhancement of guanidine neuromuscular facilitation

The effects of an intensive short-term triamcinolone diacetate pretreatment regimen (8 mg/kg intramuscularly once daily for 7 days) on the facilitation of neuromuscular transmission produced by either intravenous or direct intraarterial administration of guanidine hydrochloride, were examined in the in vivo cat soleus nerve-muscle preparation. The ability of guanidine to activate a stimulus-bound repetitive after discharge (SBR) of soleus motor axons and to produce an obligatory enhancement of soleus muscle isometric contractile tension was measured in glucocorticoid-treated vs. untreated animals. Triamcinolone pretreatment significantly increased the guanidine-induced soleus contractile potentiation by 3 to 4 times with i.v. injection ( P < 0.05) and by more than 30 times with i.a. administration ( P < 0.01). The incidence of SBR in normal motor axons after i.v. guanidine was 58.5% in the treated animals and 25.0% in the untreated ones ( P < 0.001). Also, the rate of development of the peak SBR incidence was almost doubled as a result of triamcinolone pretreatment ( P < 0.05). This glucocorticoid enhancement of the facilitatory actions of guanidine may have relevance for the treatment of certain neuromuscular disorders.

Effects of calcium and pH on the mechanical performance of heart muscle in the frog, Rana temporaria, during anoxia and subsequent recovery.

Heart ventricular muscle strips from Rana temporaria recover their isometric contractile tension completely within 20 min of reoxygenation following an anoxic period of 60 min in a physiological solution at pH 7.6. Corresponding recovery at pH 6.6 is only 43% of pretreatment values. High calcium concentration during the period of anoxia at pH 6.6 and subsequent recovery, returns contractile tension to almost pre-anoxic values within 1 h. If, however, the calcium concentration is increased at the moment of reoxygenation, contractile tension is restored even faster than if high calcium levels were present during anoxia. The loss of contractile tension caused by anoxia is the same at both pH 7.6 and 6.6 with the same calcium concentration. Comparison of the velocity parameters between high and low calcium experiments always shows a greater difference for the contraction velocities than for the corresponding relaxation velocities, independently of the pH. The quotient of these two velocities is used as an index of their relative rate of change. The results are interpreted in terms of calcium and hydrogen ion competition at various subcellular structures and the different influences these ions may have on contractile tension and both contraction and relaxation velocities.

Inotropic responsiveness of atrial myocardium bathed in Tris- or bicarbonate-buffered solutions.

Atrial muscle of guinea pigs was used to study the inotropic influences of substituting a tris(hydroxymethyl)-aminomethane-buffered solution aerated with 100% O2 for a bicarbonate-buffered solution aerated with 95% O2-5% CO2 under otherwise equivalent in vitro conditions. Basal values of isometric contractile tension and its first derivative (dT/dt) were smaller and time to peak tension and time to 90% relaxation were longer in Tris- than in bicarbonate-bathed muscles. Both groups responded similarly to changes in stimulation frequently (0.1--2.2 Hz) and Ca2+ concentration (1.0--7.0 mM); however, maximal inotropic responses to these variables were smaller in the Tris-bathed atria. The negative inotropic effects of D600 and gentamicin were greater in the Tris group. Tris-bathed atria developed pulsus alternans when exposed to Mn2+ or a reduced Ca2+ concentration, whereas pulsus alternans did not occur in the bicarbonate group. A transient increase in contractility occurred in bicarbonate-bathed atria after treatment with 0.125 mM Mn2+, but only a negative response occurred in the Tris group. Thus important, and seemingly Ca2+-dependent, differences exist between the inotropic influences of Tris and bicarbonate solutions that may affect the utility of Tris-buffered (and/or bicarbonate deprived) heart muscle for studying certain inotropic interventions.

Structural and physiological changes associated with the growth of avian fast and slow muscle.

AbstractElectron microscope examination of the myofibrillar material in the avian latissimus dorsi anterior (tonic) and posterior (phasic) muscles revealed that the characteristic felderstruktur arrangement of the tonic muscle fibers develops during growth. Fibers of embryonic and young latissimus dorsi anterior muscles up to 87 days after hatching exhibited a fibrillenstruktur arrangement. Unlike the phasic muscle fibers in which the myofibril mass splits into discrete and regularly shaped myofibrils, the myofibrils in the tonic muscle become felderstruktur in appearance because of incomplete splitting of the myofibrils. The incomplete splitting of the myofibrils and the less extensive sarcoplasmic reticulum in the tonic muscle were related to its slower rate of tension development. The isometric contractile tension of the muscles was measured and it was found to increase considerably during growth. The tension increase was directly related to the increase in the fiber size, and the myofibril content. The rate of contraction of both the latissimus dorsi anterior and posterior muscles was found to increase very rapidly just prior to hatching. After hatching, the rate of contraction of the anterior muscle decreases differentiating into a tonic muscle at one month. The latissimus dorsi posterior muscle remains fast throughout development.

Effects of monosaccharides, acetate, butyrate, lactate, and pyruvate on the developed tension of isolated rat atria.

The initial developed tension magnitude as well as the stability of the developed tension magnitude of isolated rat atria suspended in different substrates were studied. The initial developed tension was significantly greater in the presence of glucose, mannose, lactate acetate, butyrate, or pyruvate than when fructose or the nonmetabolizable monosaccharide 3-0-methylglucose was the substrate. Atrial developed tension in fructose was significantly greater than in 3-0-methylglucose or in substrate-free medium. The stability of the developed tension was comparable in 5.5 d glucose, mannose, lactate, acetate, butyrate, or pyruvate showing a small decrement with time (5-10% in 60-90 min period). Increasing concentrations of mannose, fructose, lactate, acetate, butyrate, or pyruvate up to 11.0 d did not prevent the decrement of developed tension whereas it was completely abolished in the presence of 11.0 d glucose. The ability of several substrates to modify the isometric contractile tension of rat atria suspended in KRB medium containing 5.5 mill glucose was also investigated. The addition of increasing concentrations of the metabolizable monosaccharides glucose and mannose, stimulate atrial developed tension, whereas fructose, had no effect. The 3-O-methylglucose had either no effect, or at higher concentrations resulted in a negative inotropic response. Increasing concentrations of butyrate, acetate, or pyruvate depressed the developed tension. It would appear that transport of sugars across the cell membrane or the increased formation of oxidizable substrates for the Krebs cycle are not ”per se” the only mechanism by which the metabolizable monosaccharides can maintain atrial developed tension or produce a positive inotropic effect. The possibility that the magnitude of atrial developed tension is influenced by some process that occur during the initial phases of the glycolytic sequence is discussed.

Effects of stretch on tension development in frog atrium.

Initial tension, isometric contractile tension, and the first derivative of the contractile response were recorded from the atrial wall of frog hearts. These hearts were stretched progressively from 0 to 25 g of initial tension at 25 C. Maximum peak isometric tension, maximum rate of tension development, and maximum rate of relaxation were attained at the relatively low stretching force of 2 g and at a 50% increase in length. Peak contractile tension remained near maximum under high initial tension, but the maximum rates of contraction and relaxation were markedly decreased. Stress relaxation was apparent in all preparations at all levels of initial tension. It appears to represent an alteration of the internal tension mechanism different from the alteration which accompanies the increase or decrease of the stretching force.