Fall In Tension Research Articles

Effect of temperature and velocity of stretching on stress relaxation of contracting frog muscle fibres.

1. Active muscle resists stretch with a tension greater than it can develop at constant length, but at the end of lengthening the extra tension disappears, at first rapidly and then more slowly. 2. This unexplained trend of muscle stress relaxation was studied at two different temperatures (4 and 14 degrees C) and after ramp stretches of different velocity (0.2-2.2 fibre lengths s-1) on frog muscle fibres near slack length. 3. The velocity of the fast fall in tension increases with temperature much more than that of the slow fall. In addition, the amplitude of the fast fall in tension increases with the velocity of stretching whereas that of the slow fall decreases. 4. It is hypothesized that some of the energy absorbed by the muscle during stretching is used to raise the chemical energy level of the cross-bridges, and this energy transfer occurs during and after stretching.

Phorbol 12,13-dibutyrate produces negative inotropism and selective antagonism of responses to adrenoceptor agonists in rat atria

Rat atria loaded in vitro with the dye INDO-1 produced fluorescence signals indicative of changes in cytoplasmic calcium ion concentation ([Ca 2+] c). Such atria showed systolic/diastolic fluctuations indicative of a systolic rise and a diastolic fall in both tension and [Ca 2+] c. Positively inotropic responses of the atria to isoprenaline, phenylephrine, ouabain or 4-aminopyridine were associated with fluorescence changes indicative of increased systolic increments in [Ca 2+] c. Treatment of atria with phorbol dibutyrate, on the other hand, produced negative inotropism and fluorescence changes indicative of declining systolic increments in [Ca 2+] c. Pretreating atria with phorbol dibutyrate diminished both the inotropic and fluorescence responses to subsequent treatment with phenylephrine or isoprenaline, although responses to ouabain or 4-aminopyridine were unchanged. Exposure of atria to a selective inhibitor of protein kinase C mitigated the effects of pretreatment with phorbol dibutyrate, but failed to modify responses to phenylephrine or isoprenaline that were produced in the absence of phorbol dibutyrate.

Erythropoietin--physiology and therapeutic potentialities

Erythropoietin (EPO) is the main regulatory hormone for the control of erythropoiesis. EPO leads to enhanced mitosis and differentiation of erythroid precursors in the bone marrow. The major stimulus for EPO-formation is anaemia of various origin, resulting in an exponential relation between EPO levels and a decrease in haematocrit. Another important stimulus for increased EPO production is a fall of the arterial oxygen tension caused by either cardiopulmonary disorders or by a decrease of the oxygen tension in the inspiratory gas. Human erythropoietin was first isolated and purified from a large amount of urine of patients with aplastic anaemia. After the EPO gene had been cloned and expressed, biotechnically produced recombinant human erythropoietin (rHu-EPO) became available for clinical trials. EPO deficiency appears to be the major cause of renal anaemia, and hence the treatment of these patients is the most important indication for clinical use. Encouraging results in patients whose anaemia is not of renal origin have also been reported, using treatment with rHu-EPO. In preoperative autologous blood donation programmes prior to elective surgery, rHu-EPO therapy improved the amount of donated blood and ameliorated the decrease of haematocrit values. Side effects such as hypertension, thrombosis, hypercalcaemia, elevated liver enzymes were rare and were mostly related to the underlying disease.

Relaxation rate of intact striated muscle fibres after flash photolysis of a caged calcium chelator (diazo-2).

Single twitch fibres from lumbrical muscles of Xenopus have been loaded with the photolysable calcium-chelator diazo-2 by incubation in Ringer solution containing the membrane permeable acetoxymethyl ester (AM) form of diazo-2. Incubation caused a progressive slowing of tetanus rise and relaxation which is ascribed to calcium-buffering by unphotolyzed diazo-2 (Kd = 2.2 microM). After incubation, exposure to a brief UV flash caused a three to four fold increase in the rate of tension fall. A flash given 16-18 ms after the last tetanic stimulus (at 22-24 degrees C) resulted in 10% increase in relaxation rate compared with the control before incubation. A much bigger effect was observed when a flash was given half-way into the slow phase, where an 1.8-1.9-fold increase in relaxation rate, above the preincubation slope, was observed. It is concluded that rapid lowering of [Ca]i, and hence more rapid removal of Ca2+ from troponin, speeds up relaxation, indicating that calcium translocation is the major determinant of the rate of tension fall during the isometric phase of relaxation.

Responses to hypoxia and hypercapnia in infants of substance-abusing mothers

Because infants of substance-abusing mothers (ISAM) have an increased risk of sudden infant death syndrome and have abnormal sleeping ventilatory patterns, we studied the effects of mild hypoxia during quiet sleep on ventilatory pattern, heart rate, and arousal in 23 healthy ISAM (mean +/- SEM: 9.0 +/- 0.49 weeks of age) and 15 healthy, similarly aged, control infants. Hypercapnic challenges were performed in six ISAM and eight control subjects. Hypoxic arousal responses were elicited by rapidly decreasing inspired oxygen tension to 80 mm Hg for 3 minutes or until arousal occurred. Failure to arouse to hypoxia occurred in the majority of infants in both groups. All infants had a fall in end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response. However, the fall in end-tidal carbon dioxide tension was significantly less in the ISAM (mean +/- SEM: -4.0 +/- 0.3 vs -8.0 +/- 1.0 mm Hg), suggesting blunted ventilatory responses to hypoxia. Periodic breathing occurred during 9.5% of hypoxic challenges in control infants compared with 37% in ISAM (p = 0.056). Heart rates were significantly higher in the ISAM before, during, and after hypoxic challenges. Hypercapnic challenges (inspired carbon dioxide tension of 60 mm Hg for a maximum of 3 minutes) resulted in arousal in all infants; however, ISAM required a significantly longer exposure to hypercapnia before arousal (mean +/- SEM; 116 +/- 7.8 vs 79 +/- 13.9 seconds; p < 0.02). We conclude that ISAM have an impaired repertoire of protective responses to hypoxia and hypercapnia during sleep, and that this may play a role in their increased risk for sudden infant death syndrome.

Effects of beta-adrenergic blockade on papillary muscle function and the beta-adrenergic receptor system in noninfarcted myocardium in compensated ischemic left ventricular dysfunction.

beta-Adrenergic receptor blockade has been reported to improve hemodynamics and beta-adrenergic receptor-adenylate cyclase function in idiopathic dilated cardiomyopathy. The purpose of this study was to determine the effects of beta-adrenergic receptor blockade on the beta-adrenergic receptor system and myocardial function in a model of compensated ischemic heart failure. We examined the effects of propranolol treatment on the beta-adrenergic receptor-adenylate cyclase system and isolated papillary muscle isometric function in noninfarcted left ventricular myocardium in rats after coronary artery ligation. In untreated rats with large myocardial infarction (MI), developed tension (DT) (3.0 +/- 0.7 versus 5.1 +/- 1.1 g/mm2), peak rate of tension rise (+dT/dt) (40.3 +/- 9.5 versus 71.2 +/- 12.0 g/mm2/sec), and peak rate of tension fall (-dT/dt) (24.4 +/- 5.0 versus 38.2 +/- 6.0 g/mm2/sec) were decreased (p < 0.05). In addition, DT, +dT/dt, and -dT/dt of untreated MI rats demonstrated an impaired response to isoproterenol stimulation compared with controls. beta-Adrenergic receptor density (Bmax) measured by [125I]iodocyanopindolol (ICYP) binding was decreased 23% after infarction (9.3 +/- 0.6 versus 12.0 +/- 1.8 fmol/mg protein [prot]) (p < 0.05); however, the dissociation constant (Kd) for ICYP was not changed (24.1 +/- 5.7 versus 33.2 +/- 12.1 pM). Adenylate cyclase activity in the presence of 10(-2) M MgCl2 was reduced (p < 0.05) in MI rats (30.3 +/- 10.8 versus 45.9 +/- 12.5 pmol cAMP/min/mg prot). Maximal isoproterenol (52.5 +/- 7.3 versus 79.9 +/- 10.0 pmol cAMP/min/mg prot), guanyl-5'-imidodiphosphate (GppNHp) (95 +/- 8 versus 141 +/- 25 pmol cAMP/min/mg prot) and forskolin (503 +/- 76 versus 753 +/- 157 pmol cAMP/min/mg prot) stimulation of adenylate cyclase was also decreased (p < 0.05). In addition, manganese-stimulated adenylate cyclase activity was depressed (p < 0.05) in MI rats compared with controls (23.5 +/- 2.8 versus 52.1 +/- 9.0 pmol cAMP/min/mg prot). Chronic propranolol treatment in MI rats improved DT (4.1 +/- 0.9 versus 3.0 +/- 0.7 g/mm2) and +dT/dt (54.4 +/- 11.3 versus 40.5 +/- 9.5 g/mm2/sec) (p < 0.05); however, isoproterenol-stimulated isometric function remained impaired. Propranolol treatment normalized Bmax (11.9 +/- 1.7 versus 9.3 +/- 0.6 fmol/mg prot) (p < 0.05), whereas adenylate cyclase activity remained depressed. After large MI in rats, there is impaired papillary muscle function with decreased beta-adrenergic receptors and adenylate cyclase activity in the noninfarcted myocardium. Propranolol treatment improved basal isometric muscle function and beta-adrenergic receptor density in rats after myocardial infarction but did not improve adenylate cyclase activity or isoproterenol-stimulated muscle function. These data suggest that there is a primary defect in adenylate cyclase function that persists despite upregulation of receptors with propranolol treatment.

Mechanical restitution of isolated human ventricular myocardium subjected to in vivo pressure and volume overload

The aim was to make a comparison of the mechanical and electrical refractory properties of isolated strips of human ventricular myocardium obtained from patients with either left ventricular pressure overload, volume overload, or normal left ventricular function. Strips of ventricular myocardium were obtained at the time of cardiac surgery from 17 patients with aortic stenosis, representing pressure overload, 14 patients with aortic regurgitation, representing volume overload, and nine patients with mitral stenosis, representing normal left ventricular function. Muscle strips were mounted isometrically in a tissue bath, superfused with physiological saline at 37 degrees C, and stimulated at 1 Hz. Mechanical restitution curves were constructed from the isometric twitch tension obtained from extrastimuli during a special stimulus protocol. Transmembrane action potentials were recorded using glass microelectrodes and restitution of the upstroke velocity of action potentials studied in the presence of high external potassium concentration. The aortic stenosis group was older and had higher left ventricular systolic pressures and thicker left ventricular walls than the other groups. Electrocardiographic evidence of left ventricular hypertrophy was present in both the aortic stenosis and aortic regurgitation groups. Peak tension, time to peak tension, and the maximum rates of rise and fall of tension were not significantly different between groups. The time constant of the initial rapid recovery phase of mechanical restitution (tau 1) was prolonged in the aortic stenosis group, at 603(SEM 80) ms v 367(53) ms in the aortic regurgitation group (p < 0.005), and 259(70) ms in the mitral stenosis group (p < 0.005). There was a positive correlation between tau 1 and left ventricular wall thickness (p < 0.05). Neither "normal" nor "slow" (in the presence of raised external potassium) transmembrane action potentials differed in the groups studied. The mean time constant of recovery of "slow" action potential dV/dtmax was slower in the aortic stenosis group, but this difference was not significant. These data are consistent with the hypothesis that the rate of recovery of calcium release from the sarcoplasmic reticulum is slowed in myocardial hypertrophy due to pressure overload in man and provides a possible explanation of the occurrence of mechanical alternans in such patients.

Sodium pump activation by 5-hydroxytryptamine in human placental veins

The aim of the present study was to determine the influence of the sodium pump on the responses elicited by 5-hydroxy tryptamine (5-HT) in segments of human placental veins. 5-HT (10−9−3 × 10−7M) elicited potent concentration-dependent vasoconstrictor responses, but a fall in tone was observed at higher concentrations. In the presence of 10−7 M ouabain, this fall in tension was abolished. A single concentration of 5-HT (10−6 M) produced a biphasic response, consisting in a fast early contraction followed by a slow relaxation. This relaxant phase was concentration dependently inhibited by ouabain (10−7 and 10−6 M), and abolished by preincubating the vessels in a K+-free solution and reducing bath temperature to 28°C, methods usually employed to inhibit the sodium pump. After adding 7.5 mM K+ or returning the temperature to 37°C, marked relaxation was observed. On the other hand, the relaxant phase with the amine remained unchanged by pretreatment with phenidone, oxyhemoglobin, indomethacin (all at 10−5 M) and endothelium removal. 5-HT (10−7 and 10−6M) elicited increases in ouabain-sensitivc 86Rb+ uptake. These results suggest that: (1) 5-HT activates Na+K+-ATPase, likely by an indirect mechanism that involves an increase of intracellular sodium concentration; and (2) the relaxant phase of 5-HT-evoked vasoactive responses is not mediated by the release of nitric oxide or prostacyclin from the endothelium.

Repeatability of methacholine challenge in asthmatic children measured by change in transcutaneous oxygen tension.

The airway response to bronchial provocation may be evaluated by monitoring the fall in transcutaneous oxygen tension (PtcO2) but the repeatability of this method has not been rigorously assessed. To determine the repeatability of this indirect method of assessment, bronchial challenge was performed with methacholine in nine children with stable asthma (age range 6-12 years) and was repeated 24 hours later. The response was determined by the fall both in forced expiratory volume in one second (FEV1) and in PtcO2. A modified tidal inhalation protocol was used in which quadrupling concentrations of methacholine were given, thereby reducing the time taken for the full challenge by almost half. The concentrations of methacholine that provoked a 20% decrease in FEV1 (PC20FEV1) and 15% and 10% falls in PtcO2 (PC15PtcO2, PC10PtcO2) were calculated. Repeatability measures, assessed as the 95% range for a single determination, were +/- 0.96 and +/- 1.12 doubling concentration differences respectively for PC15PtcO2 and PC10PtcO2 and +/- 0.80 for PC20FEV1. This challenge method using quadrupling concentrations and an indirect assessment of the response by PtcO2 was sufficiently repeatable for clinical use and compared favourably with repeated challenge assessed by FEV1. The PtcO2 method is simple and effort independent, and should prove particularly useful for measuring bronchial reactivity in young children.

A noninvasive assessment of myocardial oxygen tension: 19F NMR spectroscopy of sequestered perfluorocarbon emulsion.

Fluorine NMR spectroscopy of sequestered perfluorocarbon emulsion has been used to measure myocardial oxygen tension. This novel application provides a rapid noninvasive assessment of changes in oxygen tension in response to ischemia and reperfusion. Rats were predosed with Oxypherol-ET (emulsion of perfluorotributylamine). Following vascular clearance of the emulsion the heart was excised and perfused using the Langendorff retrograde technique. 19F spin-lattice relaxation time measurements provided an accurate estimate of myocardial pO2. Using a two-point determination with a time resolution of 1 s, the loss of oxygen was found to be complete within 40 s of the onset of global ischemia. The fall in oxygen tension correlated closely with an observed loss of ventricular pressure. Magnetic resonance imaging showed that perfluorocarbon was distributed throughout the heart; thus, this reporter molecule provides a global measurement of oxygen tension.

Altered myocardial force-frequency relation in human heart failure.

In congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function. The isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37 degrees C and contraction frequencies ranging from 12 to 240 per minute (min-1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfailing myocardium the twitch tension-frequency relation is bell-shaped developing 25 +/- 2 mN/mm2 at a contraction frequency of 72 min-1 and peaking at 44 +/- 3.7 mN/mm2 at a contraction frequency of 174 +/- 4 min-1. In failing myocardium the peak of the curve occurs at lower frequencies between 6 and 120 min-1 averaging 81 +/- 22 min-1, and it develops 48% (p less than 0.001) and 80% (p less than 0.001) less tension than in nonfailing myocardium at 72 and 174 min-1, respectively. Between 60 and 150 min-1 tension increases by 107% in nonfailing myocardium, but it does not change significantly in failing myocardium. Peak rates of rise and fall of isometric twitch tension vary in parallel with twitch tension as stimulation frequency rises in nonfailing myocardium but not in failing myocardium. The quantitative agreement between these results from isolated myocardium and those from catheterization laboratory measurements on intact humans suggest that alterations of myocardial origin, independent of systemic factors, may contribute to the above mentioned abnormalities in left ventricular function seen in dilated cardiomyopathy.

Changes in discharge rate of cat hamstring fusimotor neurones during fatiguing contractions of triceps surae muscles

Changes in the discharge rate of fusimotor neurones to hamstring muscles during long-lasting, fatiguing, contractions of the triceps surae muscles were studied in decerebrate cats. Discharges of fusimotor neurones were recorded from the nerve filaments. Muscle contractions were elicited by electrical stimulation of the muscle nerves applied until the muscle tension fell to about 30% of its initial value. Early and late changes could be recognized in fusimotor discharge rate. The early changes, at the onset of muscle contraction, occurred in 9 out of 22 neurones and varied in both sign and duration among the cells. The late change, encountered in 16 fusimotor neurones, was an increase in discharge rate developing towards the end of the muscle contraction and outlasting it. When the contracting triceps muscle was made ischaemic the late increase in discharge rate developed earlier, as did the muscle tension fall and started to subside after the arterial clamp was removed. After severing the muscle nerves their stimulation provoked either no changes or a slight sustained decrease in fusimotor discharge rate. It is supposed that the late increase in discharge rate of fusimotor neurones to hamstring muscles appears due to reflex excitation by discharges in group III and IV afferent fibres from the triceps muscle provoked and/or enhanced by metabolic products liberated during its fatiguing contraction. The possibility is raised that the excitation is elicited primarily by the discharges from chemosensitive afferent fibres. Its functional role in muscle fatigue is discussed.

Evidence for the presence of A1 and A2 adenosine receptors in the ventral aorta of the dogfish shark, Squalus acanthias.

Isolated, endothelium-free rings of vascular smooth muscle (VSM) from the ventral aorta of the dogfish shark, Squalus acanthias, were used to examine the vasoactive effects of various adenosine agonists. Cumulative addition of 2-chloroadenosine (2 Cl-ADO) over the concentration range 10 nM-1 mM resulted in a biphasic response, with a significant increase in tension at 1 microM and a more significant decline in tension at 100 microM and 1 mM, suggesting that this tissue may possess both A1 and A2 adenosine receptors. N6-Cyclopentyladenosine (N-6 CPA) and N6-(2-phenylisopropyl)adenosine, R(-)isomer (R-PIA), generally considered to be more A1 specific, also produced slight, but significant increases in tension, but only at relatively high concentrations. The more specific A1 agonist, N6-(25)-[2-endo-norbonyl] adenosine [(S)-ENBA] produced a significant increase in tension at 1 pM, reaching 28% above control at 10 nM. The response to (S)-ENBA was also biphasic, with a fall in tension at 10 microM. The relatively non-specific agonist 5'-N-ethylcarboxamidoadenosine (NECA) produced a small, but significant, increase in tension at 1 microM, with no subsequent decline in tension at higher concentrations. These results allow us to assign a tentative structure-activity relationship (SAR) for an increase in tension of (S)-ENBA much much greater than R-PIA greater than or equal to 2-Cl ADO = N-6 CPA = NECA; for the decrease, the SAR is (S)-ENBA greater than 2-Cl ADO greater than R-PIA greater than N-6 CPA = NECA.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotensin: dual effect on the motor activity of rat duodenum

The effects of neurotensin on mechanical activity of rat duodenum were investigated using an isometric-isovolumic preparation. Neurotensin (1 pM to 10 nM) induced a concentration-dependent, tetrodotoxin (TTX)-insensitive fall in both endoluminal pressure and isometric tension. At higher concentrations of neurotensin (1 nM to 1 μM) the relaxation was followed by a concentration-dependent TTX-insensitive contraction, detected only by an increase in endoluminal pressure. Different concentrations of neurotensin were required to desensitize the relaxant and the contractile actions of the neuropeptide. The relaxation was antagonized by apamin, while the contractile response was blocked by nifedipine. Neurotensin, when tested separately on longitudinal and circular muscular strips, caused relaxation of the longitudinal strips. Circular strips showed contractions in response to neurotensin, following an inhibitory phase, if the strips were spontaneously or pharmacologically activated. The results suggest the presence of two sets of neurotensin receptors with a differential localization between the two muscular layers in rat duodenum.

Role of nitric oxide as a mediator of internal anal sphincter relaxation

The studies were performed in in vitro to examine the role of nitric oxide (NO) in nonadrenergic noncholinergic (NANC) nerve-mediated relaxation of the internal anal sphincter (IAS) smooth muscle strips of opossums. NO caused a concentration-dependent fall in the resting tension of the IAS. The inhibitory action of NO may be exerted directly on the IAS smooth muscle since it was not modified by the neurotoxin tetrodotoxin (1 x 10(-6) M), which abolished the neurally mediated fall in the IAS tension. The inhibitor of NO synthesis NG-nitro-L-arginine (L-NNA) produced concentration-dependent suppression of the neurally mediated fall in the IAS tension. The suppression of the neurally mediated IAS relaxation was stereoselective because D-NNA had no effect on the control responses. The suppressant action of L-NNA was selectively reversed by L-arginine in a concentration-dependent manner. The reversal was complete with 3 x 10(-4) M L-arginine. D-Arginine on the other hand, at the same concentration had no effect on L-NNA-suppressed IAS relaxation. Interestingly, the fall in the IAS tension caused by vasoactive intestinal polypeptide (VIP) (an inhibitory neurotransmitter in the IAS) was also inhibited by L-NNA (3 x 10(-5) M). From these data we conclude that NO or NO-like substances serve as important inhibitory mediators for the NANC nerve-mediated IAS relaxation. A part of the inhibitory action of VIP on the IAS involves NO-synthase pathway. The exact site of formation and release of NO or NO-like substances in response to NANC nerve stimulation remain to be investigated.

Functional role of sodium pump in human placental arteries.

Ouabain (10(-7) to 10(-4) M) elicited concentration-dependent contractile responses in human placental arteries. The contractions were reduced by 10(-4) M amiloride and Ca(2+)-free medium, but not affected by 10(-6) M nifedipine or 10(-6) M Bay-K-8644, which markedly reduced or potentiated 75 nM K(+)-induced contractions, respectively. After contracting the vessels with 10(-6) M prostaglandin F2 alpha in a K(+)-free medium, the subsequent addition of 7.5 mM K+ induced a marked relaxation, which was blocked by 10(-6) M ouabain. This glycoside (10(-8) to 10(-4) M) also produced a concentration-dependent reduction of 86Rb+ uptake. Scatchard analysis of the [3H]-ouabain binding to membrane fractions from human placental arteries suggests a single class of binding sites with a KD of 88.3 nM and a Bmax of 345 fmol/mg. 5-Hydroxytryptamine (5-HT; 10(-9) to 10(-5) M) caused concentration-dependent contractions. Single concentrations produced transient responses composed of an initial contraction, followed by a slow fall in tension. Ouabain (10(-8) to 10(-6) M), K(+)-free medium or the reduction of bath temperature (28 degrees C) did not modify contractions but inhibited the relaxant phase of the response. 5-HT (10(-8) to 10(-6) M) increased both total and ouabain-insensitive 86Rb+ uptake, but the difference between them was not modified. These data indicate that: (1) human placental arteries possess an important sodium pump activity, inhibition or stimulation of which markedly alters vascular tone, (2) ouabain-evoked contractions are produced by Ca2+ entry mainly through Na(+)-Ca2+ exchange, secondary to intracellular Na+ accumulation, (3) the relaxant component of 5-HT response is dependent on the activity of the sodium pump, (4) the activation of Na+,K(+)-ATPase activity by this amine is not apparently due to direct effect, and (5) the inhibition of the sodium pump can cause long lasting increases of placental vascular resistance in the presence of physiological concentrations of 5-HT.

Energetics of calcium cycling in nonfailing and failing human myocardium.

Using sensitive antimony-bismuth thermopiles, isometric force and heat output were measured in muscle strips from nonfailing human hearts and from failing dilated cardiomyopathic hearts at a stimulation rate of 60 beats per minute (37 degrees C). This frequency was chosen because analysis of the force-frequency relation showed significant differences in isometric force between failing and nonfailing human myocardium at 60 beats per minute and at higher frequencies, whereas at lower rates of stimulation (30 beats per minute) force of contraction was similar in failing and nonfailing myocardium. The liberated initial heat was partitioned into its two components, tension-dependent heat and tension-independent heat from high-energy phosphate hydrolysis by contractile proteins and excitation-contraction coupling processes, respectively. Tension-dependent heat reflects the total number of crossbridge interactions, and tension-independent heat is an index of the amount of calcium cycling during the contraction-relaxation cycle. In failing compared to nonfailing human myocardium, peak twitch tension, maximum rate of tension rise and maximum rate of tension fall were reduced significantly. Reduced mechanical performance was associated with reduced liberation of both tension-dependent and tension-independent heat in the failing heart. The reduction of tension-dependent heat by 61% and of tension-independent heat by 69% indicate considerable decreases in the number of crossbridge interactions activated and calcium ions cycled during the isometric twitch. In addition, the rate of calcium removal was reduced in the failing human heart as is indicated by a 71% reduction in tension-independent heat rate. The efficiency of excitation-contraction coupling with respect to crossbridge activation was similar in failing and nonfailing myocardium. These data indicate that impaired myocardial performance in dilated cardiomyopathy may result from disturbed excitation-contraction coupling with reduced amount of calcium cycling and reduced rate of calcium removal.

Resuscitation from prolonged cardiac arrest with high-dose intravenous magnesium sulfate

We present evidence of resuscitation from prolonged (70-min) cardiac arrest, temporally associated with administration of 8 g intravenous (IV) magnesium sulfate (MgSO 4). A patient undergoing liposuction surgery developed bradycardia and a fall in oxygen tension after reversal of general anesthesia with physostigmine. The electrocardiogram (ECG) rhythm degenerated to ventricular asystole, which was refractory to standard therapy, including multiple boluses of epinephrine, atropine, wide-open dopamine, and attempts at right heart pacing. External cardiopulmonary resuscitation (CPR) was continuously maintained with the patient intubated on 100% oxygen. Multiple electric countershocks (× 7) and lidocaine were also administered when ventricular tachycardia/ventricular fibrillation (VTNF) occurred, but without clinical success. Approximately one hour into the resuscitation, after all of the above occurred, 8 g IV MgSO 4 was given and countershock repeated. Whereas the 7 previous countershocks had resulted in unsuccessful conversion of VT/VF to a pulseless rhythm (END), the 8th countershock (applied immediately after two 4 g boluses of IV MgSO 4) resulted in a stable pulse and normal sinus rhythm developing within 4 minutes. The patient recovered without neurologic deficit.

Effects of chronic electrical stimulation on contractile properties of long‐term denervated rat skeletal muscle.

1. The contractile properties of fast-twitch (extensor digitorum longus or EDL) and slow-twitch (soleus) muscles in the rat were followed for periods of between 4 and 10 months after denervation. The effects of chronic electrical stimulation during the last 3-8 weeks of denervation were investigated. 2. The fall in tetanic tension that follows axotomy ended after about 4 months' denervation. The equilibrium tension was about 0.75% of control tension in EDL and 0.2-0.3% in soleus. 3. The low tension in soleus was due partly to the small diameter of the muscle fibres (atrophy) and partly to their necrosis that resulted in an 8-fold fall in specific tension (the force per unit cross-sectional area). Similar but less extreme changes occurred in EDL. 4. It is speculated that the final level of tension reached by unstimulated denervated muscles is an equilibrium between decrease in force due to atrophy and necrosis and increase due to regeneration. Differences between the final tension levels in soleus and EDL cannot be accounted for quantitatively by known differences in atrophy alone. Therefore, the rate of necrosis in soleus and of regeneration in EDL may be higher. 5. Chronic stimulation of long-term denervated muscle increased force generation by about 7-fold in EDL and between 20 and 55 times in soleus. The final tension reached was between 4 and 5% of normal in both muscles. Specific tension of fibres was almost completely restored by stimulation and the number of fibres was normal. The failure to recover full tension was largely due to failure to reverse denervation atrophy completely. 6. Twitch contraction and relaxation times were identical in denervated-stimulated soleus and EDL. There was no evidence for dependence on duration of stimulation or tension of the muscle. The normalized maximum rate of rise of tetanic tension remained higher in EDL than soleus.

Constant-flow Insufflation Prevents Arterial Oxygen Desaturation during Endotracheal Suctioning

In mechanically ventilated patients, disconnection from the ventilator and endotracheal suctioning can induce major arterial oxygen desaturation resulting from apnea, changes in inspired oxygen fraction, and decrease in lung volume. The aim of this study was to test the efficacy of a simple method of delivering oxygen and maintaining lung volume during this process. Our study was conducted in two parts. In the first part, constant-flow insufflation of oxygen (CFI) was used in seven patients ventilated for acute respiratory failure (PaO2/FlO2 = 347 +/- 33 mm Hg) as a means of maintaining arterial oxygenation during apnea and disconnection from the ventilator. CFI was administered via a modified endotracheal tube in which small capillaries allowed delivery of a high-velocity jet flow near the tracheal end of the tube during disconnection from the ventilator. In comparison to apnea alone, CFI prevented a fall in arterial oxygen tension (16 +/- 7 mm Hg during CFI versus 117 +/- 27 during apnea, after 90 s of disconnection in the two situations, p less than 0.001), whereas it did not reduce the development of hypercapnia. The efficacy of CFI resulted both from the injection of oxygen into the trachea and from the maintenance of positive alveolar pressure induced by air entrainment (mean 10.4 +/- 1.1 cm H2O), preventing a fall in lung volume usually occurring after disconnection (+338 +/- 88 ml during CFI versus -344 +/- 64 ml during apnea, p less than 0.01). In the second part of the study CFI was used to prevent arterial oxygen desaturation induced by endotracheal suctioning.(ABSTRACT TRUNCATED AT 250 WORDS)