To provide an integrated assessment of changes in systolic and diastolic function in diabetic rats, we measured conscious hemodynamics and performed ex vivo analysis of left ventricular passive-elastic properties. Rats given streptozotocin (STZ) 65 mg/kg i.v. (n = 14) were compared with untreated agematched controls (n = 15) and rats treated with insulin after administration of STZ (n = 11). After 7 d, diabetic rats exhibited decreases in heart rate and peak developed left ventricular (LV) pressure during aortic occlusion. After 26 d of diabetes there were significant decreases in resting LV systolic pressure, developed pressure, and maximal +dP/dt, whereas LV end-diastolic pressure increased and the time constant of LV relaxation was prolonged. The passive LV pressure-volume relationship was progressively shifted away from the pressure axis, and the overall chamber stiffness constant was decreased. However, "operating chamber stiffness" calculated at end-diastolic pressure was increased at 7 d, and unchanged at 26 d. LV cavity/wall volume and end-diastolic volume were increased after 26 d of diabetes. Myocardial stiffness was unchanged at both time intervals. All of the above abnormalities were reversed by the administration of insulin. We conclude that the hemodynamic and passive-elastic changes that occur in diabetic rats represent an early dilated cardiomyopathy which is reversible with insulin. (J. Clin. Invest. 1990. 86:481-488.)

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This survey determined the difference in CT management among various groups of surgeons. Clinical experience was the most important factor in determining their CT strategy.

Diabetes is believed to be associated with impaired systolic and diastolic function of the heart; however, some investigators have found that diabetic rats have increased cardiac output. We investigated changes in the peripheral circulation that could account for an increased cardiac output in diabetic rats (n = 30), 4 wk after a single tail vein injection of streptozotocin (60 mg/kg), and age-matched control rats (n = 31). Compared with controls, diabetic rats exhibited decreased (P less than 0.05) mean arterial pressure, characteristic aortic impedence, and total peripheral resistance; however, cardiac index and stroke volume index were increased. Aortic compliance, mean circulatory filling pressure, central venous pressure, pressure gradient for venous return, and venous compliance were unchanged in the diabetic rats compared with control. Baseline left ventricular end-diastolic pressure and end-diastolic volume were increased in the diabetic rats. Following a volume load of 30 ml/kg, cardiac index and stroke volume index increased less in the diabetic than in the control rats (35 vs. 102% and 69 vs. 105%, respectively). Thus, even with impaired systolic function, cardiac output is increased or maintained in diabetic rats because of the combination of decreased afterload and maintenance of preload.

This review will outline cell-based therapy for heart failure focusing on tissue engineering to deliver cells to the damaged heart. We will present an overview of the central approaches focusing on pluripotent stem cell-derived cells, mechanisms of action, autologous vs. allogeneic cell approaches, immunologic modulation, and safety considerations. We will outline the progress that has been made to-date and define the areas that still need to be investigated in order to advance the field.

Age‐related variation in morphometry has been documented for many species. Knowledge of growth patterns can be useful for modeling energetics, detecting physiological influences on populations, and predicting age. These benefits have shown value in understanding population dynamics of invasive species, particularly in developing efficient control and eradication programs. However, development and evaluation of descriptive and predictive models is a critical initial step in this process. Accordingly, we used data from necropsies of 1,544 nutria (Myocastor coypus) collected in Maryland, USA, to evaluate the accuracy of previously published models for prediction of nutria age from body weight. Published models underestimated body weights of our animals, especially for ages <3. We used cross‐validation procedures to develop and evaluate models for describing nutria growth patterns and for predicting nutria age. We derived models from a randomly selected model‐building data set (n = 192–193 M, 217–222 F) and evaluated them with the remaining animals (n = 487–488 M, 642–647 F). We used nonlinear regression to develop Gompertz growth‐curve models relating morphometric variables to age. Predicted values of morphometric variables fell within the 95% confidence limits of their true values for most age classes. We also developed predictive models for estimating nutria age from morphometry, using linear regression of log‐transformed age on morphometric variables. The evaluation data set corresponded with 95% prediction intervals from the new models. Predictive models for body weight and length provided greater accuracy and less bias than models for foot length and axillary girth. Our growth models accurately described age‐related variation in nutria morphometry, and our predictive models provided accurate estimates of ages from morphometry that will be useful for live‐captured individuals. Our models offer better accuracy and precision than previously published models, providing a capacity for modeling energetics and growth patterns of Maryland nutria as well as an empirical basis for determining population age structure from live‐captured animals.

Background. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. In a previous study, tissue-engineered cardiac grafts were found to improve hosts’ cardiac electrical and mechanical functions. However, the durability of effect, immune response, and in vitro properties of the tissue graft remained uncharacterized. This present study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing evaluation of the in vitro properties of the tissue graft. Methods. hiPSC-CMs and human dermal fibroblasts were cultured into a synthetic bioabsorbable scaffold. The engineered grafts underwent epicardial implantation in infarcted immune-competent male Sprague-Dawley rats. Plasma samples were collected throughout the study to quantify antibody titers. At the study endpoint, all cohorts underwent echocardiographic, hemodynamic, electrophysiologic, and histopathologic assessments. Results. The epicardially placed tissue graft therapy improved ( p < 0.05 ) in vivo and ex vivo cardiac function compared to the untreated CHF cohort. Total IgM and IgG increased for both the untreated and graft-treated CHF cohorts. An immune response to the grafts was detected after seven days in graft-treated CHF rats only. In vitro, engineered grafts exhibited responsiveness to beta-adrenergic receptor agonism/antagonism and SERCA inhibition and elicited complex molecular profiles. Conclusions. This hiPSC-CM-derived cardiac graft improved systolic and diastolic cardiac function in immune-competent CHF rats. The improvements were detectable at seven weeks post-graft implantation despite an antibody response beginning at week one and peaking at week three. This suggests that non-integrating cell-based therapy delivered by a bioengineered tissue graft for ischemic cardiomyopathy is a viable treatment option.