Cardiac Reserve Capacity Research Articles

Abstract 18772: Transient Receptor Potential Cation Channel 6 (TRPC6) Deficiency Preserves Cardiac Mitochondrial Respiration and Attenuates Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by diastolic dysfunction, cardiac hypertrophy and mitochondrial (MT) dysfunction. TRPC6, a non-selective cation channel that mediates Ca 2+ influx, is expressed in the heart and has been suggested to regulate MT function and participate in pathological cardiac hypertrophy. However, the role of excessive TRPC6 activation in HFpEF is unclear. Hypothesis: We hypothesized that TRPC6 deficiency would attenuate generation of MT-derived reactive oxygen species (ROS), MT dysfunction, and cardiac dysfunction in a model of HFpEF. Methods: HFpEF was induced in TRPC6 knock out (KO) and wild-type (WT) control mice via a combination of high-fat diet (45% fat) and L-NAME (0.5 g/L in drinking water) administration for 10 consecutive weeks. Cardiac function was assessed using echocardiography under normal conditions and after dobutamine (DOB)-induced stress (0.75 μg/g i.p). At the end of the study, MT oxygen consumption rate and MT-ROS generation were examined in isolated cardiac fibers using OROBOROS respirometry. Results: After 10 weeks of HFD+L-NAME, WT mice developed diastolic dysfunction and cardiac hypertrophy, whereas TRPC6 KO mice exhibited preserved diastolic function (IVRT: 21.5±1.1 vs 16.3±1.2 msec and E/E’: -35±2 vs -31±2 in WT and TRPC6 KO, P <0.05). During DOB stress test (10 mins after DOB injection), TRPC6 KO mice had greater increases in stroke volume (3.3±2.8 vs -2.7±2.0 μl, P <0.05) and fractional shortening (10.4±2.8 vs 2.4±3.1%, P <0.05) from baseline compared to WT mice. TRPC6 KO mice treated with HFD+L-NAME also exhibited higher MT oxygen consumption (136.7± 31.1 vs 101.1± 20.1 pmol/min/mg, P <0.05) and lower MT-ROS generation (0.43±0.3 vs 1.46±0.5 pmol/min/mg, P <0.05) compared to WT mice treated with HFD+L-NAME. Conclusions: This study demonstrates that TRPC6 deficiency attenuated diastolic dysfunction while preserving cardiac reserve capacity, improving MT respiration, and reducing MT-ROS generation in HFpEF induced by HFD+L-NAME. Targeting TRPC6 and its downstream signaling pathways may offer a promising therapeutic approach for future HFpEF treatments.

Analysis and recognition of post-exercise cardiac state based on heart sound features and cardiac troponin I.

Excessive intensity exercises can bring irreversible damage to the heart. We explore whether heart sounds can evaluate cardiac function after high-intensity exercise and hope to prevent overtraining through the changes of heart sound in future training. The study population consisted of 25 male athletes and 24 female athletes. All subjects were healthy and had no history of cardiovascular disease or family history of cardiovascular disease. The subjects were required to do high-intensity exercise for 3days, with their blood sample and heart sound (HS) signals being collected and analysed before and after exercise. We then developed a Kernel extreme learning machine (KELM) model that can distinguish the state of heart by using the pre- and post-exercise data. There was no significant change in serum cardiac troponin I after 3days of load cross-country running, which indicates that there was no myocardial injury after the race. The statistical analysis of time-domain characteristics and multi-fractal characteristic parameters of HS showed that the cardiac reserve capacity of the subjects was enhanced after the cross-country running, and the KELM is an effective classifier to recognize HS and the state of the heart after exercise. Through the results, we can draw the conclusion that this intensity of exercise will not cause profound damage to the athlete's heart. The findings of this study are of great significance for evaluating the condition of the heart with the proposed index of heart sound and prevention of excessive training that causes damage to the heart.

Loss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling.

AimsAutophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.Methods and resultsRT–qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-specific Atg5-knockout mice (Atg5−/−). Before manifesting cardiac dysfunction, Atg5−/− mice showed compromised cardiac reserve in response to β-adrenergic stimulation. Consequently, effort intolerance and maximal oxygen consumption were reduced during treadmill-based exercise tolerance testing. Mechanistically, cellular imaging revealed that Atg5 deprivation did not alter spatial and functional organization of intracellular Ca2+ stores or affect Ca2+ cycling in response to slow pacing or upon acute isoprenaline administration. However, high-frequency stimulation exposed stunted amplitude of Ca2+ transients, augmented nucleoplasmic Ca2+ load, and increased CaMKII activity, especially in the nuclear region of hypertrophied Atg5−/− cardiomyocytes. These changes in Ca2+ cycling were recapitulated in hypertrophied human cardiomyocytes. Finally, ultrastructural analysis revealed accumulation of mitochondria with reduced volume and size distribution, meanwhile functional measurements showed impaired redox balance in Atg5−/− cardiomyocytes, implying energetic unsustainability due to overcompensation of single mitochondria, particularly under increased workload.ConclusionLoss of cardiac Atg5-dependent autophagy reduces mitochondrial abundance and causes subtle alterations in subcellular Ca2+ cycling upon increased workload in mice. Autophagy-related impairment of Ca2+ handling is progressively worsened by β-adrenergic signalling in ventricular cardiomyocytes, thereby leading to energetic exhaustion and compromised cardiac reserve.

INDIVIDUALIZED SPORTS MANAGEMENT SCHEME FOR PREGNANT WOMEN IN CHINA

In recent years, pregnant women in China generally face problems such as unbalanced and excessive nutrition, lack of proper exercise during pregnancy, which shows a significant increase in weight during pregnancy, leading to an increasing trend of perinatal complications. At present, there is less sports health management system for pregnant women throughout pregnancy. In view of this, based on the existing research in related fields, this study deeply explores the appropriate monitoring methods of pregnant women’s sports in China. In this study, effective and convenient testing methods and evaluation criteria were proposed for pregnant women’s sports and psychology. The research idea was a method based on the pulse wave to detect pregnant women’s cardiac reserve capacity, and grading the Diastolic/Systolic value of pregnant women as a reference for grading individualized target heart rate range of moderate intensity exercise. The effective time and energy expenditure of pregnant women were assessed by monitoring the exercise process. The purpose is to help and guide pregnant women in the whole process of pregnancy self-movement management, and thus improve the quality of maternal health care services in China.

Physical Exercise and Selective Autophagy: Benefit and Risk on Cardiovascular Health.

Physical exercise promotes cardiorespiratory fitness, and is considered the mainstream of non-pharmacological therapies along with lifestyle modification for various chronic diseases, in particular cardiovascular diseases. Physical exercise may positively affect various cardiovascular risk factors including body weight, blood pressure, insulin sensitivity, lipid and glucose metabolism, heart function, endothelial function, and body fat composition. With the ever-rising prevalence of obesity and other types of metabolic diseases, as well as sedentary lifestyle, regular exercise of moderate intensity has been indicated to benefit cardiovascular health and reduce overall disease mortality. Exercise offers a wide cadre of favorable responses in the cardiovascular system such as improved dynamics of the cardiovascular system, reduced prevalence of coronary heart diseases and cardiomyopathies, enhanced cardiac reserve capacity, and autonomic regulation. Ample clinical and experimental evidence has indicated an emerging role for autophagy, a conservative catabolism process to degrade and recycle cellular organelles and nutrients, in exercise training-offered cardiovascular benefits. Regular physical exercise as a unique form of physiological stress is capable of triggering adaptation while autophagy in particular selective autophagy seems to be permissive to such cardiovascular adaptation. Here in this mini-review, we will summarize the role for autophagy in particular mitochondrial selective autophagy namely mitophagy in the benefit versus risk of physical exercise on cardiovascular function.

Sirt3 Deficiency Shortens Life Span and Impairs Cardiac Mitochondrial Function Rescued by Opa1 Gene Transfer.

Aims: Sirtuins, a family of NAD+-dependent deacetylases, are recognized as nondispensable regulators of aging processes. Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase that maintains mitochondrial bioenergetics, an essential prerequisite for healthy aging. In this study, using Sirt3 knockout (Sirt3-/-) mice, we sought to establish whether Sirt3 deficiency affected life span, an endpoint that has never been tested formally in mammals, and uncover the mechanisms involved in organ damage associated with aging. Results:Sirt3-/- mice experienced a shorter life span than wild-type mice and severe cardiac damage, characterized by hypertrophy and fibrosis, as they aged. No alterations were found in organs other than the heart. Sirt3 deficiency altered cardiac mitochondrial bioenergetics and caused hyperacetylation of optic atrophy 1 (OPA1), a SIRT3 target. These changes were associated with aberrant alignment of trans-mitochondrial cristae in cardiomyocytes, and cardiac dysfunction. Gene transfer of deacetylated Opa1 restored cristae alignment in Sirt3-/- mice, ameliorated cardiac reserve capacity, and protected the heart against hypertrophy and fibrosis. The translational relevance of these findings is in the data showing that SIRT3 silencing in human-induced pluripotent stem cell-derived cardiomyocytes led to mitochondrial dysfunction and altered contractile phenotype, both rescued by Opa1 gene transfer. Innovation: Our findings indicate that future approaches to heart failure could include SIRT3 as a plausible therapeutic target. Conclusion: SIRT3 has a major role in regulating mammalian life span. Sirt3 deficiency leads to cardiac abnormalities, due to defective trans-mitochondrial cristae alignment and impaired mitochondrial bioenergetics. Correcting cardiac OPA1 hyperacetylation through gene transfer diminished heart failure in Sirt3-/- mice during aging. Antioxid. Redox Signal. 31, 1255-1271.

Post-Exercise Oxygen Uptake Recovery Delay: A Novel Index of Impaired Cardiac Reserve Capacity in Heart Failure

ObjectivesThis study sought to characterize the functional and prognostic significance of oxygen uptake (VO2) kinetics following peak exercise in individuals with heart failure (HF). BackgroundIt is unknown to what extent patterns of VO2 recovery following exercise reflect circulatory response during exercise in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MethodsWe investigated patients (30 HFpEF, 20 HFrEF, and 22 control subjects) who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and a second distinct HF cohort (n = 106) who underwent noninvasive cardiopulmonary exercise testing with assessment of long-term outcomes. Fick cardiac output (CO) and cardiac filling pressures were measured at rest and throughout exercise in the initial cohort. A novel metric, VO2 recovery delay (VO2RD), defined as time until post-exercise VO2 falls permanently below peak VO2, was measured to characterize VO2 recovery kinetics. ResultsVO2RD in patients with HFpEF (median 25 s [interquartile range (IQR): 9 to 39 s]) and HFrEF (28 s [IQR: 2 to 52 s]) was in excess of control subjects (5 s [IQR: 0 to 7 s]; p < 0.0001 and p = 0.003, respectively). VO2RD was inversely related to cardiac output augmentation during exercise in HFpEF (ρ = −0.70) and HFrEF (ρ = −0.73, both p < 0.001). In the second cohort, VO2RD predicted transplant-free survival in univariate and multivariable Cox regression analysis (Cox hazard ratios: 1.49 and 1.37 per 10-s increase in VO2RD, respectively; both p < 0.005). ConclusionsPost-exercise VO2RD is an easily recognizable, noninvasively derived pattern that signals impaired cardiac output augmentation during exercise and predicts outcomes in HF. The presence and duration of VO2RD may complement established exercise measurements for assessment of cardiac reserve capacity.

(306) - LVAD Weaning Protocol Utilizing Comprehensive Cardiopulmonary Exercise Testing to Define Cardiac Reserve Capacity

The optimal protocol for determining whether adequate LV recovery has taken place to permit LVAD explantation is not well established. Peak VO2 (pVO2) is typically the only exercise parameter utilized. We developed a protocol that integrates hemodynamic, imaging, and gas exchange measures at rest, during LVAD speed reduction, and during exercise to characterize cardiac reserve capacity and guide LVAD explant decisions. A 44 year old male with LVEF 14% demonstrated no LV recovery after CABG and required insertion of a BTT Heartware LVAD on post-op day 14. After 6 months, LVAD speed reduction to 2000 rpm led to borderline-acceptable echo parameters (LVEF 49%, LVEDD 58 mm) and a pVO2 of only 14.6 ml/kg/min. We measured VO2, peripheral O2 extraction (Ca-vO2), Fick cardiac output (CO) and pulmonary wedge pressure (PCWP) each minute during an incremental ramp exercise protocol. Exercise CO increased appropriately (7.4 to 14.6 L/min) and PCWP increment was modest (+7mmHg), which prompted us to explant the LVAD. In contrast, a 61 year old patient with a BTT LVAD demonstrated a similar pVO2 (14.1 ml/kg/min). Unlike our first patient, exercise CavO2 was normal, but he was able to augment his CO to only 8.3 L/min with a 15 mmHg increase in PCWP. LVAD explant was therefore not pursued and he underwent cardiac transplantation. Nearly identical pVO2 values in our patients with divergent relative contributions of CO and CavO2 highlight the need to consider both central cardiac and peripheral O2 extraction components of pVO2. Serial measurements of PCWP in relation to CO were particularly informative based on a 2-fold PCWP-CO slope (1.5 vs. 3.1 mmHg/L/min) in the patient not explanted. Our findings suggest that reliance on LVAD explant criteria of a pVO2 > 16 mL kg/min may not adequately reflect reserve capacity and sustained recovery potential of the native heart. Enhanced phenotyping during exercise merits further investigation to refine LVAD explant criteria.

Elevated pulmonary arterial and systemic plasma aldosterone levels associate with impaired cardiac reserve capacity during exercise in left ventricular systolic heart failure patients: A pilot study

Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aimed to characterize ET-1 and transpulmonary aldosterone levels in HFrEF and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO2). Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively. Radial ET-1 levels (median [interquartile range]) were higher in HFrEF patients compared with controls (17.5 [11.5-31.4] vs 11.5 [4.4-19.0] pg/ml, p = 0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] - radial arterial levels) was present in HFrEF (p < 0.001) but not in controls (p = 0.24). Compared with controls, aldosterone levels (median [interquartile range]) were increased in HFrEF patients in the PA (364 [250-489] vs 581 [400-914] ng/dl, p < 0.01) and radial compartments (366 [273-466] vs 702 [443-1223] ng/dl, p < 0.001). Akin to ET-1, a transpulmonary increase (median [interquartile range]) in aldosterone concentration was also observed between controls and HFrEF patients at rest (7.5 [-54 to 40] vs 61.6 [-13.6 to 165] ng/dl, p = 0.01) and peak exercise (-20.7 [-39.6 to 79.1] vs 25.8 [-29.2 to 109.3] ng/dl, p = 0.02). The adjusted pVO2 correlated inversely with aldosterone levels at peak activity in the PA (r = -0.31, p = 0.01) and radial artery (r = -0.32, p = 0.01). These data provide preliminary evidence in support of increased transpulmonary aldosterone levels in HFrEF and suggest an inverse relationship between circulating aldosterone and pVO2. Future prospective studies are needed to characterize the functional effects of transpulmonary and circulating aldosterone on cardiac reserve capacity in HFrEF.

Abstract 17780: Pulmonary Arterial Aldosterone Levels Associate with Impaired Cardiac Reserve Capacity During Exercise in Left Ventricular Systolic Heart Failure Patients

Elevated pulmonary arterial aldosterone levels (PA-ALDO) are associated with decreased exercise capacity in pulmonary hypertension patients despite normal left ventricular (LV) function. Pulmonary endothelial ALDO synthesis occurs in vitro under experimental conditions akin to LV systolic heart failure (HFrEF); however, the relevance of PA-ALDO to the clinical profile of HFrEF is not known. Therefore, we analyzed PA and radial arterial plasma in control and HFrEF patients to assess for transpulmonary ALDO release and determine if circulating ALDO is related to hemodynamic indices of cardiac reserve capacity during exercise. Data from 20 controls (51 ± 13 y, 13 females, LVEF=0.66 ± 0.9, volume of oxygen uptake at peak exercise [pVO2]=94.1 ± 11.5 % predicted) and 42 consecutive HFrEF patients (57 ± 13 y, 20 females, LVEF=0.36 ± 0.1, pVO2=47.1 ± 2.5 % predicted) undergoing invasive cardiopulmonary exercise testing were analyzed. At rest, HFrEF patients had increased PA-ALDO (714 ± 450 vs. 380 ± 187 ng/dl, P&lt;0.001) and radial ALDO levels (796 ± 483 vs. 371 ± 175 ng/dl, P&lt;0.001) compared to controls. Transpulmonary ALDO release (radial ALDO - PA-ALDO) was increased significantly in HFrEF at rest (+82 ± 20, P=0.02) and a trend was present with exercise (+62 ± 21, P=0.08). Although in controls, transpulmonary ALDO release levels were not significantly increased at rest (-9 ± 8, P=NS) or with exercise (+48 ± 13, P=NS), levels differed significantly between groups at rest and exercise (P&lt;0.05 for both). By contrast, an incremental increase at peak exercise was present in PA-ALDO by 16.3% (P&lt;0.01) and 9.2% (P&lt;0.02) for controls and HFrEF patients, respectively, but there was no significant change in levels between groups. We next explored the relationship between ALDO and cardiovascular reserve capacity measures. After controlling for age and weight in the overall cohort, resting PA-ALDO levels correlated with pVO2 (Spearman coefficient -0.37, P&lt;0.01), peak cardiac output (-0.36, P&lt;0.01), and resting mean PA pressure (0.36, P&lt;0.01). Collectively, these findings identify transpulmonary ALDO release as a novel characteristic of HFrEF and suggest that increased PA-ALDO in patients merits further investigation as a potential marker of impaired cardiac reserve capacity.

Maternal High‐Fat Diet Causes Cardiac Dysfunction and Increased Endotoxin Sensitivity in Offspring in Mice

"The fetal origins hypothesis" has been recognized for decades. The relationship between nutritional uptake and fetal cardiovascular development has not been defined. We hypothesized that maternal high‐fat diet (HFD) affects innate immunity, and thereby predisposes the offspring to cardiovascular disease in adulthood. Female C57BL/6 mice were fed with either control diet (CD) or HFD while breeding and 3 weeks after delivery. Cardiac profiles were assessed in offspring at 5‐week with echocardiogram. Offspring were then given a single dose of bacterial endotoxin (LPS, 1mg/kg, ip). Plasma serum amyloid A (SAA) levels were measured with ELISA at 0, 2h, and 24h after treatment. There were no differences on total‐, LDL‐cholesterol, and triglycerides between control and prenatal HFD offspring. While basal heart rate, cardiac output, and LV fractional shortening (FS) showed no differences, offspring exposed to prenatal HFD had significant less isoproteronol (2.5 mg/kg, ip) induced increases of FS (p&lt;0.05), indicating a reduced cardiac reserve capacity. An elevation of plasma SAA level was detected at 24h after LPS treatment (p&lt;0.001), which was more significant in mice with prenatal HFD. We concluded that maternal HFD has permanent effect on cardiac function in offspring especially under stress. It also causes an increase in LPS sensitivity, which could be explained by altered innate immunity.

Tibetans Retained Innate Ability Resistance to Acute Hypoxia after Long Period of Residing at Sea Level

Could the intrinsic characteristics of tolerance to hypoxia be retained in Tibetan high-altitude natives after they had migrated to a low altitude? To answer this question, we undertook a study of 33 healthy male adolescent Tibetans born and raised in a high plateau (3,700 m [12,140 ft] above sea level) who migrated to Shanghai (sea level) for 4 years. Ten age-matched healthy male Han adolescents born and raised in Shanghai were regarded as the control group. Acute hypoxia was induced in a hypobaric chamber for 2 h to simulate the 3,700 m altitude. At sea level, maximal oxygen consumption (VO2 max) was not significantly different between the two groups. During acute hypoxia, the values of VO2 max, tissue oxygen extraction, arterial oxygen pressure, and the arterial oxygen saturation showed markedly higher in Tibetan subjects than in Han subjects (1.41 +/- 0.04 l/min/M2 vs.1.25 +/- 0.04 l/min/M2, 55.0 +/- 4.2% vs. 47.3 +/- 9.1%, 7.2 +/- 0.6 vs. 5.5 +/- 0.2 kPa, and 87.9 +/- 3.3% vs. 78.2 +/- 1.6%, respectively, P < 0.05). The calculated "oxygen reserve capacity" and "cardiac reserve capacity" were better in the Tibetans than in the Han natives (P < 0.05), which suggests that physical work capacity is greater in the Tibetan group. The sympathetic stimulation was less, and there was no noticeable change in cardiac function during acute hypoxia in the Tibetan group. The results indicate that the better tolerance to hypoxia in the Tibetans is retained during the 4-year stay at sea level, implying that the intrinsic hypoxic adaptation still exists in the Tibetan high-altitude natives.

Maintaining serum response factor activity in the older heart equal to that of the young adult is associated with better cardiac response to isoproterenol stress

To understand the effect of transcription regulation in modulating cardiac aging, we sought to study the role of serum response factor (SRF), a key transcription factor in the heart that is normally increased with senescence and also in congestive heart failure. A Tet-Off gene expression system was used for cardiac-specific over-expression of a mutant SRF protein. In these binary transgenic mice, there is no age-related increase in SRF protein expression; in fact, there appeared to be a mild reduction of SRF protein (Mild-R SRF Tg). The older, middle-aged (15 mo) Mild-R SRF Tg mice appeared healthier and were better able to maintain their left ventricular systolic pressure (LVSP) in response to moderate â-adrenergic stimulation compared with age-matched Non-Tg mice, which demonstrated a negative ionotropic response. The Mild-R SRF Tg hearts had lower mRNA expression of BNP (p < 0.05), and the sodium calcium exchanger (p < 0.05), compared to Non-Tg. Mild-R SRF Tg had higher mRNA levels of SERCA2 (p < 0.05) and ryanodine receptor 2 (p < 0.05) compared to Non-Tg hearts. These findings suggest that preventing the age-associated increase in SRF is associated with better preserved intracellular calcium handling and functional response to stress; it might be advantageous for the older adult heart. This mouse model could be helpful in elucidating the molecular mechanisms underlying certain age-related changes in cardiac reserve capacity and response to stress.

Intravenous Anesthesia for the Patient with Left Ventricular Dysfunction

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.

Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease.

The preceding article in this series1 reviewed evidence as to why age-associated changes in the central arterial system are risky with respect to vascular disease. In a similar vane, the focus of this article is on the potential link between age-associated changes in the heart and clinical cardiac disease outcomes. Left ventricular hypertrophy, heart failure, and atrial fibrillation increase dramatically with age (Figure 1). The prevalence of left ventricular hypertrophy (LVH) also increases with rising blood pressure and body mass index, a measure of obesity.2–4 Whether identified by electrocardiography or echocardiography, left ventricular hypertrophy has been shown to be associated with increased risk for coronary heart disease, sudden death, stroke, and overall cardiovascular disease.4,5 Figure 1. A, Prevalence of echocardiographic left ventricular hypertrophy (LVH) in women according to baseline age and systolic blood pressure. B, Prevalence of echocardiographic LVH in men according to baseline age and systolic blood pressure. Both A and B are reprinted from Levy D, Anderson KM, Savage DD, et al. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors: the Framingham Heart Study. Ann Intern Med . 1988;108:7–13. C, Prevalence of heart failure by age in Framingham Heart Study men (light bars) and women (dark bars). Reprinted from Ho KK, Pinsky JL, Kannel WB, et al. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993;22:6A–13A. D, Prevalence of AF by age in subjects from the Framingham Heart Study. Reprinted from Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke . 1991;22:983–988. It has been increasingly appreciated that the development of heart failure with apparently preserved systolic function, as evidenced by a “normal” ejection fraction, occurs in about one-third to one-half of older patients with heart failure.6–9 In a …

Experimental studies on the pathogenesis of damage in the heart.

Radiation-induced heart disease has been observed in a significant number of patients following mediastinal radiotherapy of Hodgkin’s disease or postoperative radiotherapy of breast cancer. Following higher radiation doses and especially following treatments delivering a particularly high dose to the anterior pericardium, a reversible exudative pericarditis can occur within the first 2–3 years (Pierce et al. 1969; Byhardt et al. 1975; Gottdiener et al. 1983; Greenwood et al. 1974; Applefeld and Wiernik 1983). A compilation of clinical data has shown that the incidence of pericarditis rises sharply with radiation dose to the anterior pericardium (Schultz-Hector 1991a). Since modern radiation techniques achieve a more homogeneous dose distribution, pericarditis has become a rare event and is no longer a major clinical concern (Carmel and Kaplan 1976; Watchie et al. 1987; Morgan et al. 1985). With increasing survival times, particularly in Hodgkin patients, late radiation effects on myocardial function have been observed. In a significant number of patients, left ventricular ejection fractions were reduced at 5–25 years postirradiation (Morgan et al. 1985; Burns et al. 1983; Savage et al. 1990; Gomez et al. 1983). Although these patients were asymptomatic, one has to assume that the cardiac reserve capacity, i.e., the ability to compensate for cardiac stress of other origin, is reduced in these patients. We therefore developed an animal model to study the pathogenesis of radiation-induced myocardial dysfunction.

Studies on Pulmonary Circulation by &lt;SUP&gt;131&lt;/SUP&gt;I Radiocardiography.

The pulmonary circulation time measured by the right heart catheterization actually includes the circulation time from the left ventricle to an arm where the blood sample is taken. Therefore, it does not represent the accurate pulmonary circulation time. It is not accurate as well to measure the pulmonary blood volume by the right heart catheterization.The radio-cardiogram obtained by the use of radio-isotope records two peaks on its curve, the one representing the time when the isotope used is passing through the right heart, and the another representing the time when it passing through the left heart. Thus obtained pulmonary circulation represents the circulation time from right to left heart and is much more accurate. It is called ""R-L time"".To avoid the inaccuracy of the traditional dye dilution method, the pulmonary circulation time was measured from the radio-cardiogram obtained by the use of 131I. Method Total of 44 cases were studied, including 7 normal subjects, 20 cases of pulmonary diseases and 17 cases of cardiac diseases.On the chest of a patient in supine position, a scintilation detector was placed at the center of the cardiac siluette under fluoroscopy or at the center of the absolute cardiac dullness. 20 to 60 μc of 131I diluted with 0.3 to 1.1 cc of normal saline was instantly injected into cubital vein and radiocardiogram was obtained by the use of scintilation counter and scintilation ratemeter, from which R-L time was measured. Immediately afterward cardiac output was measured by the dye dilution method and the pulmonary blood volume was calculated according to the formula of Stewart-Hamilton. Hemodynamic changes by exercise were also observed in these patients.Result and Conclusion 1) Means of resting R-L time were 3.9 sec. in normal subject, 7.7 sec. in mitral stenosis, 5.2 sec. in hypertension, 5.7 sec. in coronary disease, 4.3 sec. in pulmonary tuberculosis, 4.7 sec. in bronchial asthma, 5.1 sec. in bronchiectasis and 5.3 sec. in pulmonary emphysema. This shows that the pulmonary circulation time was markedly prolonged in cardiac disease even at rest.2) Pulmonary blood volume calculated from the R-L time was much lower than that from the dye dilution method.3) By exercise, R-L time was altered along with changes in mean circulation time measured by the dye dilution method. In most of the cases, R-L time was shorted when mean circulation time was shortened, and R-L time was prolonged when mean circulation time was prolonged.4) By exercise, R-L time was shortened, cardiac output was increases and pulmonary blood volume was slightly decreased in healthy subjects and in pulmonary diseases. On the contrary, in many cases of cardiac diseases, especially in coronary disease, R-L time was prolonged, cardiac output was decreased and pulmonary blood volume was slightly increased. In cardiac disease, already increased pulmonary blood volume at rest was more increased by exercise and pulmonary congestion developed consequently.5) The prolongation of the R-L time by exercise suggests decreased reserve capacity of the heart. To know the cardiac reserve capacity, the method is recommendable as a non-operative procedure which can be done easily and repeatedly.