Search

Background Idiopathic pulmonary arterial hypertension (IPAH) is a disease characterized by progressively increased resistance of pulmonary arteries. In this study, we evaluated the mechanical property of single pulmonary artery smooth muscles cells (PASMC) from patients with IPAH and tested whether the PASMC showed abnormal response to a vasodilator by use of an atomic force microscope (AFM). Methods PASMC were isolated and cultured from explanted lungs of 7 patients with IPAH (IPAH-PASMC). Normal vascular specimens from 3 patients with bronchogenic carcinoma were used as normal controls (normal PASMC). The nano/micro-order elasticity of five to ten living PASMC in each sample was measured by parabolic force curves of cantilever deflection/indentation obtained by using an AFM. The elasticity measurements were performed under control conditions and under condition of nitric oxide (NO) treatment (190 and 380 nmol/L). Results There was no significant difference between nano/micro-order elasticity of normal PASMC and that of IPAH-PASMC under the control conditions. In normal PASMC, NO (190 and 380 nmol/L) significantly reduced (i.e., softened) the nano/micro-order elasticity. However, NO did not reduce elasticity in IPAH-PASMC, indicating higher vasodilator-resistive nano/micro-order rigidity in IPAH-PASMC. Conclusion Nano/micro-order elasticity change in PASMC in response to vasodilation induced by NO is reduced in patients with IPAH.

We developed a pH/CO 2 sensor system using two ion-sensitive field effect transistors (ISFETs) to evaluate the metabolic activity of cultured cells. One ISFET measures total pH changes and the other ISFET, covered with a gas-permeable silicon tube, measures pH changes due to CO 2 . These ISFETs were placed in a flow-through chamber with a window to be attached to a glass plate on which cells were cultured. Measurements were performed with a baseline solution of low buffer capacity. In the quantitative estimation of cellular products, we assumed that cells secreted CO 2 , lactic acid and sodium bicarbonate ( NaHCO 3 ), and then lactic acid and NaHCO 3 proceeded to the neutralization reaction to form sodium lactate and additional CO 2 . We applied this system to evaluate the metabolic activity of bovine aortic endothelial cells (BAEC) and rabbit aortic smooth muscle cells (RASMC). The production of CO 2 by RASMC was significantly higher than that by BAEC (204 ± 16 and 4.1 ± 0.3 × 10 8 molecules/cell/s, respectively). More NaHCO 3 than lactic acid was produced in RASMC, whereas they were not significantly different in BAEC.

Background Cardiac function of non–heart-beating donors (NHBDs) is uncertain due to severe myocardial damage. We developed an isolated myocardial perfusion system to resuscitate NHBD hearts and attempted to predict functional recovery of 60-minute warm ischemic hearts by analyzing systolic and diastolic functions. Methods Hypoxic cardiac arrest was induced in 8 mongrel dogs without any pre-treatments. After 60-minute ischemia, intracoronary microthrombi were flushed out by retrograde blood cardiopledia with tissue-type plasminogen activator. Coronary arteries were initially perfused from the aortic root with tepid hyperkalemic blood (20 mmol/liter) at low pressure (20 mm Hg) for the first 60 minutes and then with normothermic blood for the next 60 minutes. After 120 minutes of reperfusion, pre-load was increased for ejection against an after-load of 80 mm Hg. Pressure–volume loops were recorded to obtain the end-systolic pressure–volume relationship (ESPVR) and end-diastolic pressure–volume relationship (EDPVR). Stroke volume at a given pre-load was calculated from averaged ESPVR, EDPVR and after-load identical to an averaged baseline value. The Frank–Starling relationship was obtained and cardiac status was classified according to Forrester’s hemodynamic sub-set. Results End-systolic elastance decreased significantly to about 60% of baseline and the time constant of isovolumic relaxation was prolonged significantly by about 20%. Cardiac index was decreased to about 50% and cardiac status was classified in the Forrester III or IV sub-set. Conclusions The extent of functional recovery of NHBD hearts is predictable by cardiac output. Although 120 minutes of recovery time may be short for 60-minute ischemic damage, this system may be feasible to predict post-transplant cardiac function before transplantation.

Background Better protective effects of Celsior on cardiac function than the other conventional solutions have been reported in acute experiments and in clinical trials for at-risk patients. However, no study has yet precisely elucidated how these preservation solutions affect cardiac mechanoenergetics. Therefore, we evaluated the effects of St. Thomas' Hospital solution No. 2, University of Wisconsin solution, and Celsior on left ventricular contractility (E max : end-systolic pressure–volume ratio) and oxygen consumption. Methods We used 32 canine excised cross-circulated hearts. Twenty-three hearts served as donor hearts after hypothermic ischemia with one of the three solutions, and the remaining 9 served as controls. After arrest with each solution, the hearts were preserved for 4 hours at 4°C. Then, we measured left ventricular pressure, volume, and oxygen consumption to obtain E max and the relation between ventricular pressure–volume area (a measure of total mechanical energy) and oxygen consumption. We also evaluated the oxygen cost of E max by changing E max with calcium administration. Results Celsior did not significantly affect E max (6.3 ± 2.4 in control versus 5.3 ± 1.3 mm Hg · mL −1 · 100 g with Celsior) nor the oxygen cost of E max (1.2 ± 0.6 versus 1.6 ± 0.5 mL O 2 · mL · mm Hg −1 · beat −1 · 100 g −2 , respectively). In contrast, St. Thomas' Hospital and University of Wisconsin solutions significantly decreased E max (4.5 ± 1.1 and 3.5 ± 0.9 mm Hg · mL −1 · 100 g, respectively) and increased the oxygen cost of E max (2.5 ± 0.8 and 2.4 ± 0.9 mL O 2 · mL · mm Hg −1 · beat −1 · 100 g −2 , respectively) compared with control and Celsior-preserved hearts. The slope and intercept of the oxygen consumption versus pressure–volume area relation showed no significant difference among the four groups. Conclusions Celsior showed better protective effects on cardiac mechanoenergetics than St. Thomas' Hospital and University of Wisconsin solutions in the acute phase of heart transplantation.

Objective If the geometric distortion during dilated heart failure could be corrected, the tension on the myocytes would be decreased, thereby leading to an improvement in left ventricular systolic function. We tested the effects of the CardioClasp (CardioClasp Inc, Pine Brook, NJ), a left ventricular reshaping device, on the failing heart, and our empirical data were compared with computationally derived data. Methods Heart failure was induced by 4-week rapid cardiac pacing. At the terminal experiment, an isolated failing heart preparation (isovolumic contraction, n=5) or an intact failing heart in vivo (n = 7) was used. The effects of the reshaping device on left ventricular performance were assessed by the slopes (Ees) of the left ventricular end-systolic pressure-volume relations, hemodynamics, and echocardiograph before and after placing the CardioClasp on the heart. The change in Ees as the result of left ventricular reshaping was also estimated from computed theoretical analysis and compared with empirical data. Results There was a significant change in left ventricular dimension after placing the CardioClasp on the heart. In isolated heart preparation, Ees significantly increased from 1.40 ± 0.44 mm Hg/mL to 2.42 ± 0.63 mm Hg/mL after placing the device on the heart but returned to the baseline level (1.46 ± 0.27 mm Hg) after removing it. Left ventricular developed pressure and left ventricular fractional area shortening were significantly increased as the result of left ventricular reshaping. Ees derived from computed theoretical analysis was highly correlated with confirming empirical data. Conclusions The CardioClasp can reshape the left ventricle and improve left ventricular systolic performance in failing hearts. 17,22

Background: Hypoxia reduces cardiac contractile performance. However, there is no direct observation on how preload affects the actinmyosin-interaction (AMI) in beating hearts during hypoxia. Purpose: The aim of this study is to investigate this theme using X-ray-diffraction (XRD) analysis at a third-generation synchrotron radiation facility. Methods: Eight isolated isovolumically contracting rat hearts were paced at 120 bpm after complete heart block, mounted so that the X-ray beam (15.0 keV) passed the deeper layer of left ventricular (LV) free wall, and perfused with Tyrode solution bubbled with 100%O2(Normo) or 100%N2(Hypo). We recorded XRD patterns and LV pressure (LVP) at end-diastolic LVP (EDP) of 0 and 20 mmHg. Results: Under Normo, increasing EDP significantly increased the developed-LVP (EDP0: 104±26mmHg vs. EDP20: 141±25mmHg, p