Reconsidering Basic: Integrating Social and Behavioral Sciences to Support Learning.

PURPOSE: The integration of basic science mechanistic knowledge (pathophysiology and etiology) with clinical features (signs and symptoms) during learning leads to robust cognitive representations in novices and supports the development of clinical reasoning, including better diagnostic accuracy and later learning of related concepts. However, previous studies have used a limited scope of traditional biomedical sciences, including biochemistry, anatomy, and physiology. The use of extended forms of foundational knowledge, including behavioral and sociological sciences, that have been proposed to support learning and performance in complex health systems remains unexplored. METHOD: Thirty-three first-year medical students from the University of Toronto MD Program participated in the study. The effect of integrated extended basic science (EBS) learning was compared with that of clinically focused instruction on an initial assessment of diagnosis using clinical vignettes and a "preparation for future learning" assessment (PFLA) to assess learning of new related content in medical psychiatry (co-occurring physical and mental health conditions). RESULTS: Both forms of instruction supported the development of diagnostic ability on initial assessment (t[30] = 1.20, P = .24). On the PFLA, integrated instruction of extended forms of basic science led to superior performance on assessing complex patients' health care needs (t[30] = 2.70, P < .05). CONCLUSIONS: Similar to previous studies using integration of biomedical sciences, the integration of EBS can enhance later learning of new related concepts. These results have implications for curriculum design to support development of expert clinical reasoning.

Pediatric cardioplegia strategy results in enhanced calcium metabolism and lower serum troponin T.

BACKGROUND: Pediatric myocardium is unique from mature myocardium; thus, the use of adult cardioplegia for pediatric cardiac operations may provide suboptimal myocardial protection. We evaluated our standard adult cardioplegia (AC; modified Buckberg) and a pediatric cardioplegia (PC) solution (del Nido solution, Baxter) in vitro in rat cardiomyocytes and compared short-term outcomes in pediatric cardiac surgical patients. METHODS: Contractions, intracellular calcium, and action potentials were recorded from isolated rat cardiomyocytes exposed to PC or AC, followed by reperfusion. Pediatric patients (n = 118) undergoing cardiac operations using PC (group PC, n = 59) or AC (group AC, n = 59) were matched 1:1 for age, diagnosis, and duration of cardiopulmonary bypass. RESULTS: PC-perfused rat ventricular cardiomyocytes had lower diastolic calcium during cardioplegia and early reperfusion than AC-perfused cardiomyocytes. Cardiomyocytes remained excitable despite introduction of AC but not PC. The mean age in each pediatric group was 3.7 years (range, 3 days to 17 years; p = 0.95). Median serum troponin T levels at intensive care admission were significantly lower in group PC (0.83 +/- 0.25 microg/L) than in group AC (13.8 +/- 12.7 microg/L, p = 0.0001), which persisted at 24 hours postoperatively. There were no significant differences in duration of intubation or length of stay in intensive care or the hospital. CONCLUSIONS: Pediatric cardioplegia is associated with reduced intracellular diastolic calcium during arrest and reperfusion and more complete arrest during exposure in rat cardiomyocytes. Pediatric patients receiving pediatric cardioplegia had reduced troponin T release compared with those receiving adult cardioplegia.

Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts.

The impact of ischemic preconditioning (IPC) on contraction, Ca(2+) homeostasis, and cell survival was compared in isolated ventricular myocytes from young adult ( approximately 3 mo) and aged ( approximately 24 mo) male Fischer-344 rats. Myocytes were field stimulated at 4 Hz (37 degrees C). Contraction (edge detector) and intracellular Ca(2+) (fura-2) were measured simultaneously. Viability was assessed with trypan blue. All cells were exposed to 30 min of simulated ischemia followed by reperfusion. Some cells were preconditioned by exposure to 5 min of simulated ischemia before prolonged ischemia. Pretreatment with IPC abolished postischemic contractile depression, inhibited diastolic contracture, and increased Ca(2+) transient amplitudes in reperfusion in young adult and aged cells. IPC did not affect the modest rise in diastolic Ca(2+) in ischemia in young adult myocytes. However, IPC abolished the marked rise in diastolic Ca(2+) observed in ischemia and early reperfusion in aged myocytes. IPC also suppressed mechanical alternans in ischemia in aged cells, but younger myocytes showed little evidence of mechanical alternans whether or not cells were preconditioned. IPC markedly improved cell viability in reperfusion in young adult but not aged cells. These results suggest that IPC augments the recovery of contractile function in reperfusion by increasing Ca(2+) transient amplitudes in ventricular myocytes from young adult and aged rats. IPC reduced diastolic Ca(2+) accumulation in ischemia in aged myocytes, which may diminish the severity of mechanical alternans in aged cells. Nonetheless, the efficacy of IPC is compromised in aging, as IPC did not improve survival of aged myocytes exposed to ischemia and reperfusion.

Effects of ischemia and reperfusion on isolated ventricular myocytes from young adult and aged Fischer 344 rat hearts.

This study examined the impact of age on contractile function, Ca(2+) homeostasis, and cell viability in isolated myocytes exposed to simulated ischemia and reperfusion. Ventricular myocytes were isolated from anesthetized young adult (3 mo) and aged (24 mo) male Fischer 344 rats. Cells were field-stimulated at 4 Hz (37 degrees C), exposed to simulated ischemia, and reperfused with Tyrode solution. Cell shortening and intracellular Ca(2+) were measured simultaneously with an edge detector and fura-2. Cell viability was assessed by Trypan blue exclusion. Ischemia (20-45 min) depressed amplitudes of contraction equally in isolated myocytes from young adult and aged animals. The degree of postischemic contractile depression (stunning) was comparable in both groups. Ca(2+) transient amplitudes were depressed in early reperfusion in young adult and aged cells and then recovered to preischemic levels in both groups. Cell viability also declined equally in reperfusion in both groups. In short, some cellular responses to simulated ischemia and reperfusion were similar in both groups. Even so, aged myocytes exhibited a much greater and more prolonged accumulation of diastolic Ca(2+) in ischemia and in early reperfusion compared with myocytes from younger animals. In addition, the degree of mechanical alternans in ischemia increased significantly with age. The observation that there is an age-related increase in accumulation of diastolic Ca(2+) in ischemia and early reperfusion may account for the increased sensitivity to ischemia and reperfusion injury in the aging heart. The occurrence of mechanical alternans in ischemia may contribute to contractile dysfunction in ischemia in the aging heart.