Increased Heart Work Research Articles

The effect of propranolol on post-accident stress and clinical outcomes of burn patients: a clinical trial

Objective:
 The hypermetabolic response has undoubtedly evolved to help survive burns, but this physiological response has inconsistent consequences and increases the clinical consequences, such as increased heart work and ultimately its decline, decreased immune system function, risk of sepsis, increased long-term hospitalization, which increases the mortality of patients. This study aims to examine the effect of propranolol on post-traumatic stress disorder and clinical outcomes in burn patients.
 Methods:
 This was an open-labeled randomized clinical trial in a single center with two parallel groups without placebo control. Propranolol was given 48 hours after starting of resuscitation.
 Results:
 In this study, the burn wound of the patients who used propranolol healed faster. In addition, the administration of propranolol reduced the size of the burning surface, the size of the tissue required skin graft, the rejection rate of skin grafts, and also the length of stay in the hospital.
 Conclusion:
 Using propranolol in treating burns can play an influential role in the recovery of burn patients, and reduce the post-traumatic stress disorder.

Myocardial glucose and lactate metabolism during rest and atrial pacing in humans

There is minimal in vivo data in humans evaluating myocardial substrate utilization during increased heart work. This study was performed to determine the balance of myocardial glucose and lactate metabolism during rest and increased heart work induced by atrial pacing in seven healthy men and women (age, 49.7 +/- 3.9 years; body mass index, 23.4 +/- 1.1 kg m(-2), maximum oxygen consumption, 35.5 +/- 3.0 ml kg(-1) min(-1), ejection fraction, 68 +/- 3%). After 3 days of dietary control, catheters were placed in coronary sinus, femoral arterial and venous, and peripheral venous blood vessels. Subjects received a primed continuous infusion of [3,3,3-(2)H]lactate and [6,6-(2)H]glucose throughout the study. Arterial and coronary sinus blood sampling and measurements of coronary sinus blood flow were made during rest and atrial pacing at approximately 111 beats min(-1). Myocardial oxygen consumption increased (P = 0.04) from rest to atrial pacing. Net glucose uptake increased (P = 0.04) from rest to atrial pacing with unchanged fractional extraction (rest: 9.1 +/- 2.7%, atrial pacing 9.8 +/- 2.9%). The percentage of whole body glucose disposal from myocardial uptake also increased from rest to atrial pacing. Isotopically measured lactate uptake also increased significantly from rest to atrial pacing with no significant differences in fractional extraction. The myocardium released lactate throughout the experiment, which increased significantly from rest and atrial pacing (P < 0.05). The heart accounted for a significantly greater percentage of whole body lactate disposal during atrial pacing (15.0 +/- 4.4%) compared to rest (4.9 +/- 0.9%, P = 0.03). These data suggest: (1) in the absence of ischaemia the myocardium is constantly taking up and releasing lactate at rest which increases during atrial pacing, and (2) when arterial substrate delivery is unchanged, increased myocardial work is accomplished with similar proportions of glucose and lactate utilization in healthy humans in vivo.

Myocardial FFA metabolism during rest and atrial pacing in humans

There is limited in vivo data in humans evaluating myocardial fat utilization during increased heart work. This study was done to determine myocardial free fatty acid (FFA) metabolism during rest and atrial pacing, which increases cardiac work without changing arterial substrate concentration. We studied seven healthy men and women (age = 49.7 +/- 3.9 yr, BMI = 23.4 +/- 1.1 kg/m(2), Vo(2max) = 35.5 +/- 3.0 ml.kg(-1).min(-1), ejection fraction = 68 +/- 3%). After 3 days of dietary control, coronary sinus, femoral arterial and venous, and peripheral venous catheters were placed. Subjects received [(13)C]bicarbonate followed by a continuous infusion of [1-(13)C]palmitate through the end of the study. Arterial and coronary sinus blood sampling and measurements of resting coronary sinus blood flow were made during rest and atrial pacing to 120 beats/min. MVo(2) increased (P < 0.05) from rest to atrial pacing. Coronary sinus FFA concentration was significantly lower than arterial through rest and atrial pacing (P = 0.007). Isotopically measured myocardial palmitate uptake increased significantly from rest to atrial pacing (P = 0.03). Approximately one-third of palmitate delivery was extracted by the myocardium during rest and atrial pacing. Myocardial V(13)CO(2) production and palmitate oxidation increased significantly from rest (P < 0.01) to atrial pacing. Net glycerol balance was significantly greater than zero during rest (P = 0.04) but not different from zero during atrial pacing (P = 0.13). These data suggest that myocardial lipid uptake and oxidation increase with greater heart work during atrial pacing, with a similar relative proportion of fat oxidation to total myocardial energy expenditure.

Myocardial Ischemia and Increased Heart Work Modulate the Phosphorylation State of Eukaryotic Elongation Factor-2

Protein synthesis, in particular peptide chain elongation, is an energy-consuming biosynthetic process. AMP-activated protein kinase (AMPK) is a key regulatory enzyme involved in cellular energy homeostasis. Therefore, we tested the hypothesis that, as in liver, it could mediate the inhibition of protein synthesis by oxygen deprivation in heart by modulating the phosphorylation of eukaryotic elongation factor-2 (eEF2), which becomes inactive in its phosphorylated form. In anoxic cardiomyocytes, AMPK activation was associated with an inhibition of protein synthesis and an increase in phosphorylation of eEF2. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), did not mimic the effect of oxygen deprivation to inhibit protein synthesis in cardiomyocytes or lead to eEF2 phosphorylation in perfused hearts, suggesting that AMPK activation did not inhibit mTOR/p70 ribosomal protein S6 kinase (p70S6K) signaling. Human recombinant eEF2 kinase (eEF2K) was phosphorylated by AMPK in a time- and AMP-dependent fashion, and phosphorylation led to eEF2K activation, similar to that observed in extracts from ischemic hearts. In contrast, increasing the workload resulted in a dephosphorylation of eEF2, which was rapamycin-insensitive, thus excluding a role for mTOR in this effect. eEF2K activity was unchanged by increasing the workload, suggesting that the decrease in eEF2 phosphorylation could result from the activation of an eEF2 phosphatase.

Regulation of fatty acid oxidation of the heart by MCD and ACC during contractile stimulation.

We tested the hypothesis that the level of malonyl-CoA, as well as the corresponding rate of total fatty acid oxidation of the heart, is regulated by the opposing actions of acetyl-CoA carboxylase (ACC) and malonyl-CoA decarboxylase (MCD). We used isolated working rat hearts perfused under physiological conditions. MCD in heart homogenates was measured specifically by (14)CO(2) production from [3-(14)C]malonyl-CoA, and ACC was measured specifically based on the portion of total carboxylase that is citrate sensitive. Increased heart work (1 microM epinephrine + 40% increase in afterload) elicited a 40% increase in total beta-oxidation of exogenous plus endogenous lipids, accompanied by a 33% decrease in malonyl-CoA. The basal activity and citrate sensitivity of ACC (reflecting its phosphorylation state) and citrate content were unchanged. AMP levels were also unchanged. MCD activity, when measured at a subsaturating concentration of malonyl-CoA (50 microM), was increased by 55%. We conclude that physiological increments in AMP during the work transition are insufficient to promote ACC phosphorylation by AMP-stimulated protein kinase. Rather, increased fatty acid oxidation results from increased malonyl-CoA degradation by MCD.

Does Normovolemic Hemodilution Decrease Myocardial Oxygen Consumption Despite Increased Heart Work?

Does Normovolemic Hemodilution Decrease Myocardial Oxygen Consumption Despite Increased Heart Work?

Does Normovolemic Hemodilution Decrease Myocardial Oxygen Consumption Despite Increased Heart Work?

Does Normovolemic Hemodilution Decrease Myocardial Oxygen Consumption Despite Increased Heart Work?

Does Normovolemic Hemodilution Decrease Myocardial Oxygen Consumption Despite Increased Heart Work?

Does Normovolemic Hemodilution Decrease Myocardial Oxygen Consumption Despite Increased Heart Work?

Heart and lung adaptations to pregnancy and lactation in a crocidurine shrew

Heart and lung mass, rate of oxygen consumption (V̇ O 2 ), respiration rate (f r), tidal volume ( Vt), and heart rate (f h), were measured at rest and thermoneutrality in the shrew Crocidura russula monacha [(This shrew is claimed to be Crocidura suaveolens (Catzeflis, F., T. Maddalena, S. Hellwing and P. Vogel (1985). Unexpected findings on the taxonomic status of East Mediterranean Crocidura russula auct. (Mammalia, Insectivora). Zeitschrift fur Säugetierkunde 50: 185–201)] in nullipar (N), pregnant (P) and lactating (L) females. The heart mass of N females is large (0.86% of body mass) but f h is slow (70% of that expected by mammalian allometry), while lung mass is small (87% of expected) and f r is high (47% above expected). The 31% higher than expected expired ventilation (V̇ e) matches the 25% higher than expected V̇ O 2 . In P females the f h of 560 min −1 did not change but it increased in L females to 620 min −1. V̇ e did not change in P females but decreased in L females from 11.3 ml · min −1 to 10.1 ml min −1. The normal Vt decreased in P and L females from 47.3 μl to 38.4 μl and 37.8 μl respectively. The lower than expected resting f h of N females may provide sufficient scope for increased heart work and oxygen supply during exercise. The large heart may be more efficient. Hyperventilation in N females is indicated by the calculated relatively high fractional concentration of oxygen in expired air ( Fe O 2 ), and low fractional concentration of CO 2 in expired air ( Fe CO 2 ) (17.7% and 3.2% respectively), the high oxygen partial pressure in alveolar gas ( Pa O 2 ) and low alveolar CO 2 ( Pa CO 2 ), 119 and 34 Torr respectively, which facilitate O 2 transport through the lung air-blood barrier. The elevated V̇O 2 in P and L females is achieved by increased respiratory efficiency from the normal 15%, to 24% and 29% respectively.

Decreased rates of release of atrial natriuretic peptide from isolated hearts from aging hypertensive rats.

We tested the hypothesis that in genetically hypertensive New Zealand rats left ventricular hypertrophy predisposes to left atrial disease and should be associated with a decreased release of atrial natriuretic peptide (ANP) in response to acute left atrial stretch. Abrupt distention of the left atrium was achieved by the acute onset of left atrial distention in Langendorff-perfused isolated rat hearts, which resulted in a rapid release of ANP in all groups of hearts. Comparisons were made between normotensive and hypertensive hearts using rats aged 2 months, 8 months, 12 months, and 16 months. Rates of release of ANP from normotensive and hypertensive hearts were similar at 2 months. Thereafter, there was a progressive impairment of ANP release, until in rats aged 16 months, rates of release achieved in hypertensive hearts 2 min after the onset of left atrial distention were only about half of those of normotensive hearts (55%, P < .005). At all ages above 2 months, hypertensive hearts failed to increase the concentration of ANP in the coronary effluent at the onset of increased heart work. Therefore, in rats with genetic hypertension, there is an impairment of release of ANP from the isolated heart in response to left atrial distention.

Effects of Increased Heart Work on Release of Norepinephrine and Ventricular Arrhythmias Following Reperfusion in the Isolated Rat Heart

The influence of increasing left atrial pressures (0.5, 1.0, and 2.0 kPa) on the incidence of ventricular arrhythmias and the liberation of prelabeled norepinephrine (3H-NE) was investigated in the isolated working rat heart. Acute regional myocardial ischemia (30 min) was produced by ligature of the left main coronary artery with subsequent release of the ligature to achieve reperfusion, which consistently provoked ventricular arrhythmias. The magnitude of regional ischemia was measured by microspheres, and the efflux of 3H-labeled NE compounds was measured in the coronary effluent. Our data show that an increase in atrial pressure enhanced reperfusion arrhythmias, but the magnitude of NE release was not directly related to the occurrence of arrhythmias. It is proposed that increased heart work has an arrhythmogenic effect by enhancing the severity of regional ischemia.

Studies on the energy metabolism in the isolated, perfused Rana ridibunda heart

In the isolated, perfused Rana ridibunda heart, the concentrations of the metabolites were measured as a function of time, under increased heart work. The changes in tissue contents of adenine nucleotides were time dependent. ADP, AMP, and inorganic phosphate levels increased simultaneously, while ATP and creatine phosphate levels decreased. The tissue contents of hexose monophosphates and citrate decreased and contents of fructose bisphosphate, lactate, and pyruvate rose. A comparison of mass action ratios with apparent equilibrium constants for the glycolytic reactions indicated that phosphoglucose isomerase, aldolase, triosephosphate isomerase, and lactate dehydrogenase reactions are close to equilibrium, while phosphofructokinase is displaced from equilibrium. During increased heart work, changes in the tissue contents of adenine nucleotides and citrate appeared to play a role in the regulation of glycolysis at the level of phosphofructokinase activity. From the results, it appears that in amphibian heart, glycolysis seems to be similar to that of mammalian heart as far as control is concerned, in spite of its structural and functional differences.

The role of adenosine in the isolatedRana ridibunda heart

In an attempt to study the metabolic role of adenosine in the amphibian heart, we perfusedRana ridibunda hearts under conditions of decreased oxygen supply or increased oxygen demand and measured the rate of adenosine appearance as well as the concentrations of adenine nucleotides. Anoxia was associated with a significant increase in the myocardial and perfusate concentration of adenosine and its degradation products, inosine and hypoxanthine, while changes were also observed in the concentrations of adenine nucleotides and creatine phosphate. Furthermore, adenosine production inRana ridibunda hearts was enhanced under conditions of increased cardiac work induced by perfusion pressure elevation. Adenosine production was inversely proportional to the energy charge value calculated from the tissue content of adenine nucleotides under conditions of anoxia and increased heart work. The results are in accordance with the proposed role of adenosine as a physiological metabolic vasodilator in the coronary circulation of the mammalian heart and support the hypothesis that adenosine can be involved in regulating blood vessel resistance inRana ridibunda heart under conditions of low myocardial oxygen tension. Thus it appears that adenosine could act as a vasodilatory substance inRana ridibunda heart.

Effects of increased mechanical work by isolated perfused rat heart during production or uptake of ketone bodies. Assessment of mitochondrial oxidized to reduced free nicotinamide-adenine dinucleotide ratios and oxaloacetate concentrations

Metabolic effects of increased mechanical work were studied by comparing isolated pumping rat hearts perfused by the atrial-filling technique with aortic-perfused non-pumping hearts perfused by the technique of Langendorff. The initial medium usually contained glucose (11 mm) and palmitate (0.6 mm bound to 0.1 mm albumin). During increased heart work (comparing pumping with non-pumping hearts) the uptake of oxygen and glucose increased threefold, but that of free fatty acids was unchanged. Tissue contents of alpha-oxoglutarate, NH4+, malate, lactate, pyruvate and Pi rose with increased heart work, but contents of ATP, phosphocreatine and citrate fell. Ketone bodies were produced with a ratio of beta-hydroxybutyrate/acetoacetate of about 3:1 in both pumping and non-pumping hearts but with higher net production rates in non-pumping hearts. When ketone bodies were added in relatively high concentrations (total 4 mm) to a glucose (11 mm) medium the medium, ratios of beta-hydroxybutyrate/acetoacetate were not steady even after 60 min of perfusion. The validity of calculating mitochondrial free NAD+/NADH ratios from the tissue contents of the reactants of the glutamate dehydrogenase system or the beta-hydroxybutyrate dehydrogenase system is assessed. The activities of these enzymes are considerably less in the rat heart than in the rat liver, introducing reservations into the application to the heart of the principles used by Williamson et al. (1967) for calculation of mitochondrial free NAD+/NADH ratios of liver mitochondria...

The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart.

1. The work of the perfused rat heart was acutely increased by raising the aortic pressure in the Langendorff preparation from 50 to 120mmHg; within 1 min in perfusions with media containing glucose or glucose+acetate, rates of oxygen consumption and tricarboxylate-cycle turnover increased 2.5-fold, glycolysis rate doubled and oxidation of triglyceride fatty acid was strikingly enhanced. 2. Increased cardiac work had no significant effects on the heart concentrations of creatine phosphate, ATP, ADP or 5'-AMP. The only significant changes in tricarboxylate-cycle intermediates were a decrease in malate in perfusions with glucose and decreases in acetyl-CoA and citrate and an increase in aspartate in perfusions with glucose+acetate. 3. Measurements of intracellular concentrations of hexose phosphates, glucose and glycogen indicated that work accelerated glycolysis by activation of phosphofructokinase and subsequently hexokinase; the activation could not be accounted for by changes in the known effectors of phosphofructokinase. 4. Acetate at either perfusion pressure increased heart concentrations of acetyl-CoA, citrate, glutamate and malate and decreased that of aspartate; acetate increased tricarboxylate-cycle turnover by 50-60% and inhibited glycolysis and pyruvate oxidation. 5. In view of the markedly different effects of acetate and of cardiac work on the concentrations of cycle intermediates the changes that accompany acetate utilization may be specifically concerned with the regulatory functions of the cycle in control of glycolysis and pyruvate oxidation and not with the associated increase in cycle turnover. It is suggested that the concentrations of key metabolites controlling the rate of cycle turnover may fluctuate with each heart beat and that this may explain why no significant changes (for example, in adenine nucleotide concentrations) have been detected with increased work in the present study.

Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats.

1. In the isolated perfused rat heart, the contractile activity and the oxygen uptake were varied by altering the aortic perfusion pressure, or by the atrial perfusion technique (;working heart'). 2. The maximum increase in the contractile activity brought about an eightfold increase in the oxygen uptake. The rate of glycolytic flux rose, while tissue contents of hexose monophosphates, citrate, ATP and creatine phosphate decreased, and contents of ADP and AMP rose. 3. The changes in tissue contents of adenine nucleotides during increased heart work were time-dependent. The ATP content fell temporarily (30s and 2min) after the start of left-atrial perfusion; at 5 and 10min values were normal; and at 30 and 60min values were decreased. ADP and AMP values were increased in the first 15min, but were at control values 30 or 60min after the onset of increased heart work. 4. During increased heart work changes in the tissue contents of adenine nucleotide and of citrate appeared to play a role in altered regulation of glycolysis at the level of phosphofructokinase activity. 5. In recirculation experiments increased heart work for 30min was associated with increased entry of [(14)C]glucose (11.1mm) and glycogen into glycolysis and a comparable increase in formation of products of glycolysis (lactate, pyruvate and (14)CO(2)). There was no major accumulation of intermediates. Glycogen was not a major fuel for respiration. 6. Increased glycolytic flux in Langendorff perfused and working hearts was obtained by the addition of insulin to the perfusion medium. The concomitant increases in the tissue values of hexose phosphates and of citrate contrasted with the decreased values of hexose monophosphates and of citrate during increased glycolytic flux obtained by increased heart work. 7. Decreased glycolytic flux in Langendorff perfused hearts was obtained by using acute alloxan-diabetic and chronic streptozotocin-diabetic rats; in the latter condition there were decreased tissue contents of hexose phosphates and of citrate. There were similar findings when working hearts from streptozotocin-diabetic rats with insulin added to the medium were compared with normal hearts. 8. The effects of insulin addition or of the chronic diabetic state could be explained in terms of an action of insulin on glucose transport. Increased heart work also acted at this site, but in addition there was evidence for altered regulation of glycolysis mediated by changes in tissue contents of adenine nucleotides or of citrate.

The Value of Lactate and Pyruvate Measurements in the Assessment of the Redox State of Free Nicotinamide-Adenine Dinucleotide in the Cytoplasm of Perfused Rat Heart.

In the isolated rat heart perfused with glucose as substrate, measurements were made of perfusate and tissue lactate and pyruvate concentrations, and of tissue α-glycerophosphate and dihydroxyacetone phosphate concentrations. The conditions studied included increased heart work, anoxia, the addition of insulin, acute alloxan diabetes, chronic streptozotocin diabetes, and the addition of ketone bodies. True intracellular lactate values (estimated from the lactate and sorbitol spaces) and apparent tissue values exceeded perfusate values, showing the existence of a lactate concentration gradient. During anoxia, the lactate gradient diminished. Cytoplasmic free NAD+/NADH ratios calculated from the extracellular lactate/pyruvate ratio were similar to and changed in the same direction as the NAD+/NADH ratios calculated from the tissue α-glycerophosphate/dihydroxyacetone phosphate ratios in non-diabetic hearts. In diabetio hearts, extracellular and tissue lactate/pyruvate ratios gave different values for the cytoplasmic free NAD+/NADH ratios than did tissue α-glycero-phoaphate/dihydroxyacetone phosphate ratios. These discrepancies were associated with accumulation of pyruvate in the perfusate and the tissue. Changes in the extracellular lactate/pyruvate ratio gave a better differentiation between acute heart work and acute anoxia than did changes in the heart lactate/pyruvate ratio. The use of extracellular lactate/ pyruvate measurements in assessing the state of myocardial oxygenation is supported by these observations, provided that nutritional factors are taken into account and the diabetic state is excluded.

The addition of cava pulmonary artery shunts to patients with existing systemic pulmonary artery shunts

I N THE LAST TWO DECADES various types of systemic pulmonary artery (S-PA) shunts have been used to palliate children with cyanotic heart lesions. Some eventually have been totally corrected, some have died as a result of their original anomaly or from complications of the shunt itself, and some continue reasonably well palliated. However, many of these patients have lesions not amenable to total correction, are poorly palliated and show signs of progressive deterioration. This report deals with this last group. In infants with noncorrectable cyanotic heart disease we would prefer to perform a Glenn shunt as the primary procedure. The high pulmonary vascular resistance and frequent hypoplastic pulmonary arteries found in these neonates both tend to inhibit blood flow from the cava to the pulmonary circuit. The delayed slip knot ligation of the azygos vein introduced by Bargeronl has allowed better results in small infants, but generally we prefer a high-pressure systemic pulmonary artery (S-PA) shunt in tiny babies if surgical intervention is necessary. The high pressure shunts commonly employed are the Potts-Smith, Waterston, and Blalock-Taussig. Potts and Waterston shunts are frequently associated with too much blood flow to the lungs resulting in increased heart work, congestive heart failure and pulmonary congestion. Blalock-Taussig shunts, on the other hand, are more frequently “outgrown” and fail to meet the patient’s needs. Increased pulmonary vascular resistance is a rare but serious complication of highpressure shunts, a problem not encountered with cava-pulmonary artery (C-PA) shunts. It seems feasible in those patients with high-pressure shunts who are deteriorating for any reason to convert to or add a Glenn (C-PA) shunt which has proven to be an excellent long-term palliative procedure for complex noncorrectable cyanotic heart lesions.2,3 Early in our experience in this series the plan was to obliterate the highpressure shunt and convert to a low-pressure C-PA shunt. Since this would have required bilateral thoracotomies in most cases we elected to simply add the C-PA shunt to the opposite lung. As experience grew it became apparent that the ideal palliation is derived from a C-PA shunt to one lung and a small S-PA

Myocardial anaerobic metabolism in intact dogs

Energy liberated from substrates of heart muscle metabolism appears as mechanical work and heat. External mechanical work and heat production of the left ventricle were compared with its oxygen consumption in intact dogs. Under control conditions, within the range of accuracy possible, the sum of work and heat was equal to energy from oxidative metabolism. Intravascular administration of cyanide increased heart work but reduced its rate of aerobic metabolism. During the cyanide effect, work plus heat exceeded the energy available from oxidative metabolism. The difference represents myocardial anaerobic metabolism. Since the energy of mechanical work output alone was greater than the myocardial aerobic energy source, a portion of the anaerobic energy liberated must have been converted to mechanical work.

電気的収縮期間に関する研究(第5報) : 第3編 心臓仕事量とQT時間との関係に就ての臨床的験証

In order to verify the experimental results on the relation between the heart work and the QT interval, reported in the preceding articles, in clinical cases, the author studied 53 hypertensive patients and 48 hypotensive patients, which were considered under no influence of digitalis, quina alkaloid and abnormal conditions of any electrolyte.(1) In the hypertensive instances without demonstrable myocardial damage (26 cases), the QT interval was longer than the normal average QT interval in all cases, moreover abnormally prolonged in the majority of cases. But in the hypertensive instances with myocardial damage (27 cases), in general, the QT interval was shortened in comparison with the QT interval in the hypertensive group without myocardial damage.(2) In the hypotensive instances without demonstrable myocardial damage (48 cases), the QT interval tended to be shortened in comparison with the normal QT interval, in general.(3) The above-mentioned clinical data are agreed with the experimental results on the toad heart reported in the preceding articles. Namely, also in the clinical cases under no influence of special medicaments, (i) when the heart function is not damaged, the QT interval is prolonged at increased heart work and is shortened at decreased heart work, and (ii), when the heart function is damaged, the QT interval is shorter than the QT interval which the healthy heart would show when it would work out the same load.(4) Consequently, it is not reasonable, either that the QT interval outside the normal limits is always interpreted to mean that the heart is functionally damaged, or that the QT interval within the normal limits is always interpreted to mean that the heart function is not damaged.The meaning of the QT interval should be interpreted in the relation to the heart work.