The Tension-time Index Research Articles

Tension-time index, fatigue, and energetics in isolated rat diaphragm: a new experimental model.

The tension-time index (TTI) has been used to estimate mechanical load, energy utilization, blood flow, and susceptibility to fatigue in contracting muscle. The TTI can be defined, for a rhythmically contracting muscle, as the product of average force development divided by maximum tetanic force times duty cycle [contraction time / (contraction + relaxation time)]. In this study, the TTI concept was applied to isolated diaphragm via a method that allowed TTI to be clamped at a predetermined value. The hypothesis tested was that, at constant TTI, muscle energetics and the extent of fatigue would vary with stimulation frequency. Isolated diaphragm strips were stimulated at 25, 50, 75, or 100 Hz for 4 min, one per second. Duty cycle was continuously adjusted to maintain TTI at 0.07, which was near the highest TTI tolerated for 4 min, at 20-Hz stimulation. At the end of the fatigue run, muscles were either immediately frozen for determination ATP, creatine, and creatine phosphate concentrations (n = 6) or stimulated for evaluation of low- and high-frequency fatigue (n = 5). Results demonstrated no difference in the extent of fatigue or in the final ATP and creatine phosphate concentrations between groups. Large within-run increases in duty cycle were required at low stimulation frequencies, but only small increases were required at the highest frequencies. The results demonstrate that, at a constant TTI, similar fatigue properties predominate at all stimulation frequencies with no clear distinction between high- and low-frequency fatigue. The method of clamping TTI during fatigue may be useful for evaluating energetics and contractile function between treatment groups in isolated muscle when treatment influences baseline contractile characteristics.

PULMONARY REPLACEMENT WITH A TOTAL ARTIFICIAL LUNG

Purpose: An oxygenator with low resistance may be perfused by the native cardiac output (CO) and serve as a Total Artificial Lung (TAL). However, the absence of compliance may increase pump load in a pulsatile system. Impedance is the resistance to pulsatile flow, and is expressed as a function of harmonic. While the zero harmonic impedance (Z9) represents the resistance to steady flow, the first harmonic (Z1) dominates the load to pulsatile flow. The tension-time index (TTI) is a correlate of myocardial oxygen consumption. We sought to characterize right ventricular (RV) load and adaptation in the setting of pulmonary replacement with a TAL. Methods: Five adult male sheep were instumented with micromanometers in the RV, proximal pulmonary artery (PA), and left atrium (LA), and an ultrasonic flow probe was placed around the proximal PA. Conduits were anastamosed to the PA and LA, and connected to a TAL. Data were obtained under two conditions: 1) conduits clamped, allowing native pulmonary circulation, and 2) distal PA occluded, diverting the total RV output through the TAL. Epicardial and intracardiac echocardiographs were obtained. The pulsatility index (PI) was calculated by dividing the amplitude of flow in the first harmonic by the CO. Results: Although CO, mean PA pressure (mPAP) and resistance were unchanged (CO: 6.2 ± 1.5 vs 5.6 ± 0.9 L/min, p=NS; mPAP: 18.5 ± 3.6 vs 18.1 ± 3.2 mmHg, p=NS; Z0: 3.1 ± 0.6 vs 3.3 ± 0.5 Woods Units, p=NS), there was a substantial increase in Z1 (0.4 ± 0.1 vs 5.8 ± 1.4 Woods Units, p<0.01). This elevated impedance was associated with an increase in the TTI from 843.5 ± 113.3 to 1032.1 ± 224.3 mmHg-s/min, p=0.04. Blood flow ejected from the right ventricle became less pulsatile, reflected by a reduction in the PI from 0.64 ± 0.12 to 0.23 ± 0.09, p<0.01. Echocardiographs suggested incomplete closure of the pulmonic valve with forward diastolic flow. In the setting of pulmonary replacement with a TAL, high impedance with unchanged resistance alters cardiac function, and may have long-term effects upon the RV. Addition of a compliance chamber can reduce Z1, and may restore normal ventricular function.

Breathlessness during induced lung hyperinflation in asthma: the role of the inspiratory threshold load.

The effects of the inspiratory threshold load (ITL) on breathlessness and ventilatory mechanics during acute bronchoconstriction were studied by comparing responses to continuous positive airway pressure (CPAP) and inspiratory positive airway pressure (IPAP) in 12 asthmatic subjects after methacholine bronchoprovocation to a maximum change (delta) in FEV1 of 50%. At maximum response, "optimal CPAP" (CPAPOPT) was selected as the level of CPAP providing maximum subjective improvement in breathlessness. Spirometry, breathing pattern, esophageal pressure (Pes), and operational lung volumes were monitored. At maximum response, FEV1 decreased by 54 +/- 3% (mean +/- SEM) (p < 0.001), dynamic end-expiratory volume (EELVdyn) increased 66 +/- 8%, by 1.4 +/- 0.2 L (p < 0.001), and subjects reported severe breathlessness (Borg Scale = 5.6 +/- 0.8). CPAPOPT (5.3 +/- 0.6 cm H2O) significantly (p < 0.001) reduced breathlessness (delta Borg Scale = -3.0 +/- 0.5) and did not cause further dynamic hyperinflation. CPAPOPT reduced peak inspiratory Pes by 27% (p < 0.001), the tension-time index (TTI) for the inspiratory muscles by 27% (p < 0.01), and the inspiratory work rate per liter of ventilation by 14% (p < 0.05). During CPAPOPT, the delivered extrinsic positive end-expiratory pressure (PEEPe) (6.4 +/- 0.4 cm H2O) was strongly related (p < 0.001) to the measured ITL (6.9 +/- 1.0 cm H2O) at maximum response. Responses to IPAP of the same magnitude as CPAP OPT at maximum response were similar to those during CPAPOPT, except that IPAP did not counteract ITL or reduce breathlessness.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of graded muscle contractions on spinal cord substance P release, arterial blood pressure, and heart rate.

The release of substance P (SP)-like immunoreactivity (SP-LI) in the dorsal horn of the spinal cord and the cardiovascular changes to both high-tension (HT) and low-tension (LT) contractions were determined using alpha-chloralose-anesthetized cats. Over a 10-minute period, seven contractions (HT or LT) were induced. Each contraction was 20 seconds in duration and was followed by an 80-second quiescent period. The tension-time index (TTI) for the HT contractions was 2751 +/- 348 kg.s (mean +/- SD), which was greater than the TTI of 813 +/- 167 kg.s for the LT contractions. The HT contractions caused a greater release of SP-LI than the LT contractions: SP-LI increased from 0.18 +/- 0.02 to 0.32 +/- 0.03 fmol/100 microL and from 0.18 +/- 0.02 to 0.25 +/- 0.04 fmol/100 microL for the two types of contractions, respectively. Concomitant with this greater SP-LI release, HT contractions caused larger increases in mean arterial pressure (34 +/- 16 versus 11 +/- 4 mm Hg) and heart rate (18 +/- 7 versus 8 +/- 4 beats per minute) than did the LT contractions. These changes in SP-LI, mean arterial pressure, and heart rate were virtually abolished when the contractions were repeated after sectioning the L-5-S-2 dorsal and ventral roots or when the electrical stimulation of the ventral roots was repeated after muscle paralysis with gallamine triethiodide. These results demonstrate that contraction-evoked SP-LI release in the dorsal horn is related to the developed tension. Furthermore, these data provide additional support for the hypothesis that the release of SP from the central terminations of muscle afferents plays a role in mediating the cardiovascular responses to static contraction of skeletal muscle.

Reduction of acute myocardial ischemia in rabbit hearts by nafazatrom.

The effects of oral nafazatrom pretreatment (10 mg/kg, twice a day, for 10 days) on myocardial ischemia were studied in the rabbit heart during 6-h occlusion of the left anterior descending coronary artery (LAD). The tension-time index (TTI), hemodynamics, and ischemia size were determined (Evan's blue-triphenyltetrazolium chloride staining with planimetry). In drug-vehicle controls, left ventricular (LV) and peripheral pressures and LV dP/dtmax decreased, while heart rate, end-diastolic pressure, the TTI, and electrocardiographic ST segments increased. Hemodynamics were nearly unaltered in the nafazatrom-pretreated animals, except for a heart rate elevation during the initial phase of LAD occlusion. In drug-treated hearts, 45 +/- 6% of the LAD perfusion region at risk was ischemic, showing a patchy distribution. In vehicle controls, 82 +/- 4% (p less than 0.02 vs. nafazatrom pretreatment) of the LAD-perfused myocardial regions was transmurally ischemic, showing a uniform pattern. Thus, nafazatrom pretreatment prevented most hemodynamic changes following LAD occlusion in the rabbit heart. Significant amounts of the muscle remained normoxic within the nonperfused arterial regions. These results indicate that the inhibition of lipoxygenase enzymes by nafazatrom may delay the development of ischemic damage to the heart following acute coronary artery occlusion.

Effect of FR 7534, a new calcium antagonist, on myocardial oxygen demand

The actions of FR 7534, a new calcium antagonist, nitroglycerin, and dipyridamole on myocardial oxygen demand have been compared. Six anaesthetized dogs received two infusion levels of each drug which produced equivalent arterial hypotension. All three compounds reduced the tension-time index (TTI). FR 7534 and nitroglycerin but not dipyridamole produced significant decreases in myocardial oxygen consumption (MV̇O 2). FR 7534 demonstrated oxygen-sparing actions comparable to nitroglycerin. FR 7534 may prove beneficial in alleviating myocardial ischemia.

The Influence of the Ventilatory Pattern on Ventilation, Circulation and Oxygen Transport during Continuous Positive‐Pressure Ventilation An Experimental Study

In IPPV, the ventilatory pattern produced by the ventilator and the lung systems is known to influence pulmonary and cardiovascular functions. In this study on dogs the ventilatory pattern of a conventional respirator (Siemens‐Elema Servo Ventilator 900=SV‐900) constituted the norm for comparison with that produced by a system for volume‐controlled HFPPV. The experimental conditions were kept identical (pentobarbital anaesthesia and normoventilation, i.e. arterial PCO2=40 mm Hg, pH=7.4 and constant FIO2 of the inspired air).At comparable alveolar ventilation the intratracheal peak and mean pressures were always higher during ventilation with SV‐900 than during HFPPV. The calculated alveolar oxygen partial pressure (PAO2) was almost identical with the two systems. The differences in arterial PCO2 and PO2 between SV‐900 and HFPPV were negligible when 30% O2 was used. The total peripheral resistance (TPR) was lower during ventilation with HFPPV, and although the cardiac output (CO) and stroke volume (SV) were greater during HFPPV, calculations of the tension‐time index (TTI) revealed no differences between the two ventilator systems. With 30% O2 the alveolo‐arterial PO2 difference (A‐aDO2) was smaller, the oxygen flux (OF) greater and the venous admixture lower during ventilation with HFPPV.The lower TPR during ventilation with HFPPV in association with a higher cardiac output and improved tissue perfusion indicates that the ventilatory pattern in volume‐controlled HFPPV interferes less with the cardiovascular functions. Thus, HFPPV appears able to give better myocardial and circulatory efficiency.

Ischemia in aortic stenosis: Hemodynamic prediction

The records of 12 patients with aortic stenosis previously studied by Fallen et al. 1 in 1967 before and after infusion of isoproterenol were reviewed to assess the value of hemodynamic indexes in predicting myocardial ischemia—defined as less than 5 percent transmyocardial lactate extraction or lactate production. Potential subendocardial blood supply was estimated from a diastolic pressure-time index (DPTI), calculated from aortic and left ventricular pressure, and oxygen demand, estimated from the tension-time index (TTI). The ratio DPTI TTI was used to estimate the supply/demand relation. Of eight patients with aortic stenosis but without associated coronary artery disease, four (Group A) metabolized lactate normally after administration of isoproterenol, and four (Group B) had biochemical evidence of ischemia. Three of four patients (Group C) with aortic stenosis and associated coronary artery disease had abnormal glycolysis after administration of isoproterenol. Calculated aortic valve areas were comparable in all groups. In patients with aortic stenosis alone, abnormal lactate metabolism occurred whenever DPTI/TTI was less than 0.30 ( P < 0.01) (Group B). Two of three patients with aortic stenosis and associated coronary artery disease (Group C) showed abnormal lactate metabolism when DPTI/TTI was greater than 0.6; this ratio was below 0.3 in the third patient. These results suggest that the supply/demand relation calculated from these readily obtained indexes may be useful (1) in predicting in which patients with aortic stenosis ischemia will develop, (2) in distinguishing the role played by associated coronary artery disease, and (3) as an adjunct to calculation of valve area since the quantitation of associated aortic regurgitation is not necessary.

Effect of propranolol on myocardial oxygen consumption and its hemodynamic correlates during upright exercise.

Measurements were made of heart rate, aortic blood pressure, systolic ejection period/beat, myocardial blood flow, and myocardial oxygen consumption in nine normal young men during three bouts of upright bicycle exercise: 1) at the workload which produced a heart rate of 120 beats/minute, 2) at the higher workload necessary to produce a heart rate of 120 beats/minute after administration of intravenous propranolol 0.25 mg/kg, and 3) with infusion of propranolol, at the same workload as the first exercise bout. Comparing exercises 1 and 2, we found a much higher workload was required to produce the same heart rate after propranolol. The blood pressure, heart rate-blood pressure product, and myocardial oxygen consumption were the same despite the much greater level of exertion. Comparing exercises 1 and 3, the heart rate, blood pressure, heart rate-blood pressure product, and myocardial oxygen consumption were all significantly lower during exercise 3 after propranolol despite the fact that the same degree of exercise was being done. As in previous studies, the heart rate-blood pressure product was an excellent correlate of myocardial oxygen consumption despite the change in contractility induced by propranolol. The systolic ejection period was prolonged significantly altering the tension-time index (TTI), which became an inadequate index of myocardial oxygen consumption. It is concluded that the heart rate-blood pressure product is a good index of myocardial metabolic needs during exercise and the relationship is undistorted by marked changes in contractility, but the tension-time index is a poor correlate. This data emphasizes the fact that the relative metabolic loads for the whole body and for the heart are determined separately and may not change in parallel with a given intervention.

Effect of isoproterenol and norepinephrine on myocardial function in experimental cardiogenic shock

Cardiogenic shock was produced in 18 dogs by the technique of closed-chest coronary embolization with plastic microspheres. Isoproterenol (0.2 μg per kilogram per minute) and norepinephrine (1.0 μg per kilogram per minute) were infused for 15-minute periods into each shocked animal, and the effects on myocardial function were compared. In the dosage employed, isoproterenol and norepinephrine caused a similar increase in both coronary blood flow and myocardial O 2 consumption. Norepinephrine had a significantly greater effect than isoproterenol in raising arterial blood pressure and in increasing left ventricular work as measured by the tension-time index (TTI). Increase in myocardial work was accompanied by a small increase in left ventricular end-diastolic pressure during infusion of norepinephrine, whereas isoproterenol caused a significant fall in this measurement. Both drugs decreased the level of arterial lactate, indicating improved systemic blood flow. Isoproterenol caused no change in the extraction of lactate by the heart, but norepinephrine, in contrast, resulted in the development of a negative A-V lactate difference across the myocardium with net lactate production by the heart, indicating increased anaerobic myocardial metabolism. These data indicate that the infusion of norepinephrine may have a deleterious effect on myocardial function when used in a dosage commonly employed in treating patients with cardiogenic shock. It is suggested that isoproterenol is equally as effective as norepinephrine in improving cardiac performance after acute myocardial infarction, and that its use is less likely to provoke increased myocardial hypoxia.

Velocity of contraction as a determinant of myocardial oxygen consumption.

In 12 dogs on right-heart bypass with heart rate, stroke volume, and aortic pressure constant, the velocity of contraction was augmented comparably by three fundamentally distinct interventions in the same heart: 1) sustained postextrasystolic potentiation produced by paired, electrical stimulation; 2) norepinephrine infusion; and 3) calcium infusion. In each instance the correlation between velocity of contraction and MVo2 was striking. During paired stimulation, maximum rate of left ventricular ejection increased by an average of 50.3% ± 3.8% (se of mean) above control, MVo2 increased by 1.96 ± 0.10 ml/100 g per min (39.8% ± 1.6% above control), while the tension-time index (TTI) fell 12.4% ± 1.1%. With norepinephrine, and with calcium, left ventricular ejection rates were increased 52.9 ± 3.2% and 55.1 ± 3.2%, respectively, and MVo2 was augmented 2.03 ± 0.08 ml/100 g per min and 1.87 ± 0.04 ml/100 g per min, while the TTI decreased 15.9 ± 0.6% and 12.4 ± 2.4%. Since MVo2 always increased substantially while TTI fell, tension cannot be considered to be the sole determinant of MVo2. Since comparable increases in velocity of contraction produced by different interventions were associated with similar large augmentations of MVo2, it appears that the velocity of contraction is an important determinant of MVo2. Furthermore, it is likely that the so-called O2 wasting effect exerted by norepinephrine on myocardial metabolism may be explained largely by an increased velocity of contraction.

冠循環調節機序に関する実験的研究

The mechanism of reactive increase of coronary blood flow (CBF) occurring during experimental coronary embolization was studied on a total of 43 closed chest dogs anesthetized with amobarbital sodium, with special reference to the myocardial oxygen consumption, myocardial energetics and neurohumoral aspects.Coronary sinus outflow was measured by electromagnetic flowmeter through Morawitz's canula. (a) Coronary embolization was produced using the suspension of Lycopodium spores and the changes in CBF were determined. In some experiments the relationships of CBF with the myocardial oxygen metabolism and cardio-dynamic indices were detected. The indices used were mean arterial pressure, cardiac work, the product of heart rate and mean arterial pressure (Katz), its modification (the product of heart rate and systolic mean pressure of left ventricle), and the tension-time index (T.T.I.) of Sarnoff. The last one is equal to the product of systolic mean pressure of left ventricle, duration of systole and heart rate. The influences of the autonomic nerves on CBF were investigated under the bilateral cervical vagotomy or bilateral cervical sympathetic ganglionectomy, and compared with the control group. (b) Coronary obstruction was produced using the catheter devised for this purpose. The reactive hyperemia occurring after the release of temporal obstruction was observed under the influences of blood pressure, section of the autonomic nerves and some drugs previously administered. (c) Effects on CBF of various substances injected into the coronary artery were investigated. Substances injected were several drugs including catecholamine, acetylcholine etc and coronary venous blood of another experimental dog collected before and after the coronary embolization.Results obtained were as follows : 1) Following the coronary embolization, CBF was temporarily decreased and then increased by an average of 40% after 3 minutes. This reaction was neither abolished by the vagotomy nor by the sympathectomy. The degrees of average increase, however, seemed to be reduced by the vagotomy and augmented by the sympathectomy; and these tendencies were thought to be the results of influences of both nervous systems upon the tenes of the coronary vessels.2) T.T.I. was proved to correlate best with the myocardial oxygen consumption among the cardio-dynamic indices (r=0.90). Thus, it was confirmed that the myocardial oxygen consumption was related to all the mechanical energy including the intracardiac tension rather than to the external effective work alone.3) Myocardial oxygen consumption was reduced compared with the T.T.I. immediately after coronary embolization, and therefere the myocardial oxygen debt was suggested to be produced. This oxygen debt was supposed to introduce the increase of CBF, and during this period the oxygen supply to myocardium far exceeded the myocardial oxygen consumption.4) Increase in CBF following the release of coronary obstruction was independent on the autonomic nerves, was related with the myocardial ischemia produced, and was limited to the local area. By the intravenous administration of eserine, the response was markedly increased. Thus, the contribution of localized myocardial metabolism, particularly of the acetylcholine-like substance, was suggested to play a very important role in the production of reactive hyperemia. Coronary dilator substance has been supposed to exist in the coronary sinus blood during the embolization, but this failed to be proved in this experiment.5) As to the reactive increase in CBF following coronary embolization, fundamentally myocardial energy requirement, that is, myocardial oxygen requirement was thought to result in the augment of myocardial oxygen supply. As the regulatory mechanism of coronary circulation which mediated such a reaction, the important role of the above-mentioned localized myocardial metabolic factor was emphasized.