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To determine whether changes in density (rho) of infarct and noninfarct zones during healing and remodeling after myocardial infarction influence estimates of left ventricular mass and detection of temporal changes by imaging, we measured weights (g) and volumes (mL) of infarct, noninfarct, and mixed tissue in hearts removed 1 to 42 days after anterior infarction in three groups of dogs: nonreperfused infarction treated with placebo or captopril, or infarcts reperfused after 2 h. In vivo mass was calculated from in vivo diastolic myocardial volumes (echocardiograms) and an assumed density of 1.05 g/mL or actual values derived from tissue weights and volumes. Over the 42 days, actual density deviated more from the assumed value of 1.05 in infarct than noninfarct zones, and the overall density was higher for reperfused than nonreperfused ventricles (1.09 vs. 1.06 g/mL, p < 0.01). Correction for density improved the correlation between absolute in vivo and postmortem mass slightly but not the detection of relative changes in mass in control, captopril, or reperfusion groups. These findings suggest that (i) densities of infarct and noninfarct zones differ and change during healing, especially after reperfusion, and (ii) correction for density provides more accurate estimates of volume-derived mass in reperfused hearts.

The P1 purinoceptor subtype mediating the negative inotropic responses of guinea-pig left atria and the negative chronotropic responses of beating right atria were characterized. Guinea-pig isolated paced left atria (2Hz, 5ms, threshold voltage+50%) and spontaneously beating right atria were set up in Krebs-bicarbonate solution and isometric tension and rate of contraction, respectively, were recorded. Concentration-response curves for the reduction of tension and rate, respectively, by adenosine receptor agonists, N6-cyclopentyladenosine (CPA), the R- and S- stereoisomers of N6-(2-phenylisopropyl) adenosine (R-PIA and S-PIA), 5'-(N-carboxamido) adenosine (NECA) and 2-p-((carboxyethyl)-phenethylamino)-5'-(N-carboxamido) adenosine (CGS21680) were obtained. The orders of potency on the left atria (CPA = NECA > R-PIA > S-PIA > CGS21680) and right atria (CPA = R-PIA > S-PIA > CGS21680) were consistent with the responses being mediated via A1 receptors. Antagonism of the responses to CPA or R-PIA by 8-cyclo-1,3-dimethylxanthine (CPT) was examined by a full Schild analysis. Concentration-response curves for CPA or R-PIA were obtained in the absence or presence of five or six concentrations (10(-7)-10(-5) or 3 x 10(-5)M) of CPT. The shift in the concentration-response by CPT was expressed as the concentration-ratio (CR) and plotted as -log(CR-1) against log molar concentration of CPT (Schild plot). pA2 values were calculated from the intercept on the concentration axis and by application of the equation; pA2 = log(antagonist concentration) -log (CR-1). The Schild plots had unity slopes indicating competitive antagonism and the pA2 values derived therefrom indicated that the responses were mediated via A1-receptor. Closer inspection of the Schild plots, however, showed that at the higher concentrations of CPT there was a limit to the displacement of the concentration-response curves of the left and right atria to CPA and of the left atria to R-PIA. There were also significant differences in the apparent pA2 values calculated from the equation, when different concentrations of antagonist were examined. These results indicated that at higher concentrations of agonist there may be a component of the response that is resistant to antagonism by CPT. Whether this is related to the proposal that cardiac responses are mediated via A3 receptors is discussed.

Background: Angiotensin II type 1 (AT1) receptor antagonists, when given over the long term, reduce the deleterious consequences of ischemia-reperfusion injury. Whether short-term administration of AT1 or angiotensin II type 2 (AT2) receptor antagonists is cardioprotective has not been investigated., Methods and Results: The effects of short-term administration of selective AT1 and AT2 receptor antagonists on the recovery of mechanical function during reperfusion after 30 minutes of global, no-flow ischemia were studied in left atrium-perfused isolated working rat hearts. Control hearts (n = 8) showed incomplete recovery of left ventricular minute work (LV work) and cardiac efficiency during reperfusion to 51 +/- 15% and 61 +/- 19% of preischemic levels, respectively. Compared with control hearts, the selective AT2 receptor antagonist PD123,319 (0.3 mumol/L) given before ischemia (n = 7) improved the recovery of LV work and efficiency to 82 +/- 4% and 98 +/- 7% of preischemic levels, respectively (P < .01). In contrast, the selective AT1 antagonist losartan (1 mumol/L) blocked the recovery of LV work and depressed efficiency to 0 +/- 0% and 1 +/- 0% (n = 7) of preischemic levels, respectively (P < .01; n = 7). Neither antagonist altered coronary vascular conductance., Conclusions: This is the first demonstration that short-term treatment with a selective AT1 versus AT2 antagonist exerts different effects on recovery of mechanical function after ischemia-reperfusion: the AT2 antagonist was cardioprotective, whereas the AT1 antagonist was not. These data suggest that AT2 antagonists and AT1 agonists may offer novel approaches for the treatment of mechanical dysfunction after ischemia-reperfusion.

The action of the adenosine agonist, 5'-(N-ethylcarboxamido)-adenosine (NECA), at extracellular A2 receptors of guinea-pig and rabbit aortic rings was investigated. A near-maximum relaxant concentration (10(-5) M) of NECA was determined from cumulative concentration-response curves in aortae precontracted with noradrenaline. The effects of this concentration of NECA upon the noradrenaline-induced contractions were measured as the ratio of the contractions obtained before and, in the same tissue, after addition of NECA. This ratio was compared with the control ratio obtained in paired tissues after adding vehicle between the first and second contraction. The roles of intracellular Ca2+ mobilization and influx of extracellular Ca2+ were examined using normal Ca2+ and Ca(2+)-free media. In normal Ca2+ medium, where both sources of Ca2+ are involved in the contraction to noradrenaline, NECA inhibited the contractions. In Ca(2+)-free conditions, the phasic contraction to noradrenaline was mediated via the intracellular Ca2+ pool and was not inhibited by NECA. The contractions of the guinea-pig aorta to angiotensin II (10(-6) M) in both normal and Ca(2+)-free media, which are mediated via release of intracellular Ca2+, were also not inhibited by NECA. These results indicate that the activation of extracellular A2 adenosine receptors by NECA does not cause vasorelaxation by interfering with the release of intracellular Ca2+ by noradrenaline. The effects of NECA on contractions, due to influx of extracellular Ca2+, were examined in guinea-pig aortae in Ca(2+)-free medium and after exposure to angiotensin to deplete intracellular Ca2+ stores. Contractions were then induced by restoring the Ca2+ to the medium. These contractions were not inhibited by NECA, but when noradrenaline was present during the restoration of Ca2+, NECA was inhibitory. This and the evidence in normal Ca2+ medium, suggests that NECA causes vasorelaxation in the aorta by interfering with the Ca2+ influx via receptor-operated channels induced by noradrenaline.

The negative inotropic responses of guinea pig isolated left atria to the P1-receptor agonists adenosine and L-N6-phenylisopropyladenosine (L-PIA), the muscarinic receptor agonist carbachol, and the potassium channel activator cromakalim were examined. The potassium channel blocker 4-aminopyridine (4-AP, 10 mM) decreased the concentration-response curve for L-N-6-phenylisopropyladenosine (L-PIA) so that the maximum reduction in atrial tension was significantly reduced from 77.8 to 61.9%. The concentration-response curve for the negative inotropic response to carbachol was displaced to the right by a substantially greater amount (521-fold), partly due to the muscarinic receptor blocking activity of 4-AP. The response to a single submaximum dose of L-PIA (520 nM) was slow in onset and monophasic, whereas adenosine induced a rapid reduction in tension followed by a gradual return toward the resting level. In the presence of 4-AP (10 mM), the peak response to L-PIA was significantly reduced from a 59.7 to 31.0% inhibition of tension. In addition, the rate of development of the response was significantly slowed. The peak inhibition of tension by adenosine (112 microM) (60.0%) was also significantly reduced to 37.4% in the presence of 4-AP (10 mM). Furthermore, there was no rapid decrease in tension but a gradual decrease to a peak effect which was no different from that in the absence of 4-AP. These results suggest that the P1-receptor agonists exert negative inotropy through a K+ channel-dependent component which is blocked by 4-AP and a slower-onset K+ channel-independent component. The potassium channel blocker, bromobenzoylmethyladamantylamine (BMA 100 microM) also shifted (11-fold) the concentration-response curve for the negative inotropic response to adenosine, and to a lesser extent that to cromakalim (2.1-fold) and carbachol. Glibenclamide (0.3, 3, and 30 microM), a selective antagonist of ATP-regulated potassium channels, was a potent antagonist of the negative inotropic responses to cromakalim. However, 30 microM failed to antagonize the responses to L-PIA, adenosine, or carbachol, indicating that they do not mediate their responses through ATP-regulated potassium channels. 4-AP (10 mM) caused a slight shift (2.3-fold) of the concentration-response curve for cromakalim, indicating weak activity against ATP-regulated potassium channels in the left atrium. This study showed that P1-receptor agonists exert negative inotropic responses in guinea pig left atria only in part through activation of potassium channels. These channels differ from the ATP-regulated potassium channels activated by cromakalim.

To combat the problem of excess capacity and to meet the needs of its elder community. Highland Park Hospital (HPH) in Highland Park, Illinois decided to convert an unused acute care unit into a skilled nursing facility (SNF). Detailed here is the methodology used to determine the number of SNF beds needed by HPH, the options for development available, and the factors considered when choosing the type of facility to be designed.

Although business and industry have been involved with the planning process for some time, hospitals have only recently realized the powerful tool that the process represents.

Because of the business community's increased involvement in the health care sector, hospitals' planning functions are beginning to resemble those of major corporations.