Biomedical subjects

P F Soto

Publications and source records attributed to P F Soto.

5 recordsLinked to original sources

PubMed2000

Improvement of rejection-induced diastolic abnormalities in rat cardiac allografts with inducible nitric oxide synthase inhibition.

OBJECTIVE: Inhibition of inducible nitric oxide synthase (nitric oxide II) activity has been proposed as a method to attenuate capillary leak and edema during rejection of heterotopically transplanted rat hearts. Myocardial edema has previously been implicated in diastolic dysfunction during allograft rejection. Accordingly, we tested the hypothesis that inducible nitric oxide synthase inhibition with aminoguanidine would alleviate left ventricular stiffening and myocardial edema formation in 4-day heterotopic rat heart allografts. METHODS: Passive left ventricular filling was studied in American Cancer Institute Lewis rats receiving heterotopic heart transplants receiving either aminoguanidine, a selective nitric oxide synthase inhibitor (n = 6); dexamethasone (1 mg. kg(-1). d(-1) administered subcutaneously) for 4 days after transplantation (n = 6); or intravenous saline solution (n = 6). American Cancer Institute-to-American Cancer Institute isografts (n = 6) were used as controls. RESULTS: Serum nitrite/nitrate levels in the aminoguanidine group (18 +/- 3 mmol/L) and dexamethasone group (22 +/- 4 mmol/L) were reduced versus the intravenous saline group (144 +/- 36 mmol/L [SEM]) to levels seen in controls (25 +/- 9 mmol/L). Left ventricular volume at 15 mm Hg for the aminoguanidine group was increased versus that for the intravenous saline solution group, similar to that for controls, and reduced versus dexamethasone-treated animals. Myocardial water content for the aminoguanidine-treated animals (78.3% +/- 0.4%) was similar to those of intravenous saline-treated animals (78.0% +/- 0. 3%) but greater than those of controls (77.1% +/- 0.2%) and dexamethasone-treated animals (76.7% +/- 0.3%). CONCLUSIONS: Nitric oxide II inhibition with aminoguanidine minimizes the reduction in left ventricular filling that is seen with allograft rejection through a mechanism that is not associated with attenuation of myocardial edema.

Animals↗

PubMed1998

Retrograde coronary perfusion: effects on iatrogenic edema and diastolic properties.

BACKGROUND: The relative merits of antegrade infusion and retrograde infusion of cardioplegic solution in terms of heart weight, myocardial water content, and ventricular diastolic properties are undefined. Accordingly, we compared antegrade and retrograde flow of hemodiluted blood in isolated, hypothermic porcine hearts. METHODS: After cardiectomy, 1 L of cold heparinized blood diluted with lactated Ringer's solution to concentrations ranging from 100% lactated Ringer's to 50% lactated Ringer's and 50% blood was perfused in an antegrade (n = 6) or retrograde (n = 6) fashion at mean pressures of 62 +/- 2 mm Hg (+/- standard error of the mean) and 49 +/- 2 mm Hg, respectively. Heart weight, myocardial water content, and left ventricular pressure-volume relationships were obtained before and after perfusion. RESULTS: In the comparison of measurements before and after perfusion, changes in heart weight (36 +/- 4 g versus 5 +/- 2 g; p < 0.05), myocardial water content (6.9% +/- 1.0% versus 2.5% +/- 0.4%; p < 0.01), and ventricular filling measured by normalized left ventricular volume at 10, 15, and 20 mm Hg were greater in the antegrade group. CONCLUSIONS: In the isolated porcine heart, retrograde flow is distinguished from antegrade flow by less change in heart weight and myocardial water content and no diastolic dysfunction.

Animals↗

PubMed1998

Diastolic properties, myocardial water content, and histologic condition of the rat left ventricle: effect of varied osmolarity of a coronary perfusate.

BACKGROUND: Although myocardial edema is known to impair diastolic filling of the left ventricle, the interrelation of edema, histologic condition, and function has not been quantitated sufficiently for extrapolation to studies of multifactorial influences on diastolic properties. METHODS: Accordingly, ACI rat hearts arrested at 4 degrees C underwent coronary artery perfusion with a cardioplegia solution that was either unaltered (288 mOsm/L, P288 group, n = 6), diluted (144 mOsm/L, P144 group, n = 6), or concentrated (380 mOsm/L, P380 group, n = 6). Postmortem left ventricular pressure-volume curves and myocardial water content were measured. Myocardial samples were fixed in varying dilutions of glutaraldehyde. After dehydration and paraffin embedding, edema was graded subjectively (0 to 5), and myocardial interstitial spaces were determined by use of a semiquantitative method. RESULTS: Mean normalized left ventricular filling volume at 20 mm Hg filling pressure in the P144 group, 189 +/- 16 microliters (SEM), was reduced versus both the P288 (278 +/- 26 microliters) and the P380 (332 +/- 18 microliters) groups (p < 0.05, ANOVA). Mean myocardial water content in the P144 group, 80.7% +/- 1%, was increased versus the P380 (76.7% +/- 0.4%, p < 0.05) but not versus the P288 group (78.4% +/- 0.8%). In hearts preserved with 2.5% glutaraldehyde, mean edema grade and interstitial space in the P144 group (4.0 +/- 0.3) were increased versus the P380 (1.8 +/- 0.3, p < 0.05) but not the P288 group (2.7 +/- 0.5). Derived linear regressions relate water content to filling volume and histologic condition. CONCLUSIONS: Coronary perfusate osmolarity is thus associated with predictable changes in myocardial water content, left ventricular filling volume, and edema. These correlations allow definition of new hypotheses for the study of cardiac allograft rejection in patients and experimental animals.

Animals↗

PubMed1998

Effect of improved myocardial protection on edema and diastolic properties of the rat left ventricle during acute allograft rejection.

BACKGROUND: Studies of myocardial edema and diastolic dysfunction in rat heart transplantation have been flawed by ischemic injury. This study uses improved methods to prevent ischemic contracture. METHODS: Hearts of 30 ACI rats were transplanted into the abdomen of Lewis rats by use of cold University of Wisconsin solution for improved preservation. Left ventricular diastolic properties were expressed as volume at standardized pressure intervals. RESULTS: On posttransplantation day 3, mean left ventricular volume at 15 mm Hg in allografts (290 +/- 9 microl, SEM) was not significantly different vs isografts (299 +/- 32 microl), allografts on day 0 (337 +/- 28 ml) or day 1 (324 +/- 20 microl), or native hearts (334 +/- 19 microl). However, volume was reduced to 173 +/- 17 microl on day 4 and to 70 +/- 23 microl on day 5 (p < 0.05). Similar findings were obtained for volume at 5 and 10 mm Hg. Allograft myocardial water content on day 3, 76.3% +/- 5%, similar to allografts on day 0 and 1 and to isografts on day 3, increased to 77.6% +/- 8% on day 4 (NS) and 79.4% +/- 6% on day 5 (p < 0.05 vs day 0). Histologically, rejection in allografts was mild on day 3, moderate on day 4, and severe on day 5. CONCLUSIONS: Reduced left ventricular filling volume during rejection is only partially explained by edema. Abnormalities of diastolic properties previously attributed to the unloaded state of nonworking heart models may actually reflect inadequate peritransplantation myocardial protection.

Adenosine↗

PubMedDate not supplied

Arterial windkessel parameter estimation: a new time-domain method.

We developed and validated a new, more accurate, and easily applied method for calculating the parameters of the three-element Windkessel to quantitate arterial properties and to investigate ventriculoarterial coupling. This method is based on integrating the governing differential equation of the three-element Windkessel and solving for arterial compliance. It accounts for the interaction between characteristic impedance and compliance, an important phenomenon that has been ignored by previously implemented methods. The new integral method was compared with four previously published methods as well as a new independent linear least-squares analysis, using ascending aortic micromanometric and volumetric flow measurements from eight dogs. The parameters calculated by the new integral method were found to be significantly different from those obtained by the previous methods but did not differ significantly from maximum likelihood estimators obtained by a linear least-squares approach. To assess the accuracy of parameter estimation, pressure and flow waveforms were reconstructed in the time domain by numerically solving the governing differential equation of the three-element Windkessel model. Standard deviations of reconstructed waveforms from the experimental ensemble-averaged waveforms, which solely reflect the relative accuracy of the Windkessel parameters given by the various methods, were calculated. The new integral method invariably yielded the smallest error. These results demonstrate the improved accuracy of our new integral method in estimating arterial parameters of the three-element Windkessel.

Animals↗