American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Oct 2010
Left ventricular underfilling and not septal bulging dominates abnormal left ventricular filling hemodynamics in chronic thromboembolic pulmonary hypertension.
Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with abnormal left ventricular (LV) filling hemodynamics [mitral early passive filling wave velocity/late active filling wave velocity (E/A) < 1]. Pulmonary endarterectomy (PEA) acutely reduces pulmonary vascular resistance, resulting in an increase of mitral E/A. The abolishment of leftward septal bulging and an increase in right ventricular (RV) output are thought to be responsible for the increase of mitral E/A. ⋯ When an exclusive decrease of mPAP was simulated, mitral E/A increased 26%, mLAP decreased 16%, and septal curvature became rightward. When an exclusive increase of CO was simulated, mitral E/A increased 53% and mLAP increased 62%, whereas leftward septal bulging persisted. Thus, our simulations suggest that the increase of mitral E/A with PEA is caused two-thirds by an increase of RV output and one-third by the abolishment of leftward septal bulging.
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Am. J. Physiol. Heart Circ. Physiol. · Oct 2010
Angiotensin-(1-7) upregulates cardiac nitric oxide synthase in spontaneously hypertensive rats.
It has been shown that angiotensin (ANG)-(1-7) activates nitric oxide synthase (NOS) in isolated ventricular myocytes from normotensive rats. Since many ANG-(1-7) actions are enhanced in situations of increased ANG II activity, as in hypertension, in this study we investigated the in vivo effect of ANG-(1-7) on NOS activity and expression of endothelial (eNOS), neuronal (nNOS), and inducible NOS (iNOS) in ventricles from spontaneously hypertensive rats (SHR). Rats were subjected to a 60-min ANG-(1-7) infusion (0.35 nmol/min); controls received saline. ⋯ Isolated ventricle slices preincubated with ANG-(1-7) showed an increase in NOS activity and eNOS phosphorylation, which was blocked by an AT(2) and a bradykinin B(2) receptor antagonist, but not by the Mas receptor antagonist. Our results show that in rats in a hypertensive state, ANG-(1-7) infusion upregulates cardiac NOS expression and activity through an AT(2)- and bradykinin-dependent mechanism. In this way ANG-(1-7) may elicit its cardioprotective action and contribute to some of the counterregulatory AT(2) receptor effects that oppose the AT(1) receptor-mediated effects.
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Am. J. Physiol. Heart Circ. Physiol. · Oct 2010
Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore.
Leptin-induced protection against myocardial ischemia-reperfusion (I/R) injury involves the activation of the reperfusion injury salvage kinase pathway, incorporating phosphatidylinositol 3-kinase-Akt/protein kinase B and p44/42 MAPK, and the inhibition of the mitochondrial permeability transition pore (MPTP). Recently published data indicate that the JAK/STAT signaling pathway, which mediates the metabolic actions of leptin, also plays a pivotal role in cardioprotection. Consequently, in the present study we considered the possibility that JAK/STAT signaling linked to the MPTP may be involved in modulating the cardioprotective actions of leptin. ⋯ This is the first study to yield evidence that JAK/STAT signaling linked to the MPTP plays a role in leptin-induced cardioprotection. Under the experimental conditions employed, STAT3 phosphorylation appears to have occurred earlier during reperfusion than that of Akt. Further research into the interactions between these two signaling pathways in the setting of I/R injury is, however, required.
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Am. J. Physiol. Heart Circ. Physiol. · Oct 2010
Cardiac function is not significantly diminished in hearts isolated from young caveolin-1 knockout mice.
Matrix metalloproteinases (MMPs) are known to degrade components of the extracellular matrix. More recently, in myocardial oxidative stress injury including ischemia-reperfusion, MMP-2 is activated and degrades troponin I and α-actinin. MMP activity is regulated at several levels. ⋯ Western blot analysis revealed no significant changes in troponin I or α-actinin between Cav-1(-/-) hearts and their controls. There was a significant loss of MMP-2 from both knockout and control hearts during the perfusion. In summary, despite the loss of Cav-1, Cav-1(-/-) hearts show similar or better cardiac function compared with wild-type hearts following physiological challenge or β-adrenergic stimulation in vitro, and this appears unrelated to changes in MMP-2.
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Am. J. Physiol. Heart Circ. Physiol. · Sep 2010
ReviewContinuous and less invasive central hemodynamic monitoring by blood pressure waveform analysis.
Blood pressure waveform analysis may permit continuous (i.e., automated) and less invasive (i.e., safer and simpler) central hemodynamic monitoring in the intensive care unit and other clinical settings without requiring any instrumentation beyond what is already in use or available. This practical approach has been a topic of intense investigation for decades and may garner even more interest henceforth due to the evolving demographics as well as recent trends in clinical hemodynamic monitoring. ⋯ We then summarize earlier techniques and thereafter overview recent techniques by our collaborators and us in greater depth while pinpointing both their strengths and weaknesses. We conclude with suggestions for future research directions in the field and a description of some potential clinical applications of the techniques.