Nitric oxide for the treatment of postpneumonectomy pulmonary edema.

Inhaled nitric oxide, a selective pulmonary vasodilator, has been used to improve arterial oxygenation in adult respiratory distress syndrome. To our knowledge, it has not been successfully used to treat this syndrome after major lung resection. We used nitric oxide to treat postpneumonectomy pulmonary edema with immediate and sustained improvement in oxygenation. The patient was successfully weaned from nitric oxide and extubated after 3 days of supportive therapy.

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.

Coronary perfusate composition influences diastolic properties, myocardial water content, and histologic characteristics of the rat left ventricle.

BACKGROUND: Recent studies found that edema, histology, and left ventricular diastolic compliance exhibit quantitative relationships in rats. Edema due to low osmolarity coronary perfusates increases myocardial water content and histologic edema score and decreases left ventricular filling. The present study examined effects of perfusate osmolarity and chemical composition on rat hearts. METHODS: Arrested American Cancer Institute (ACI) rat hearts (4 degrees C) were perfused with different cardioplegia solutions, including Plegisol (289 mOsm/L), dilute Plegisol (172 mOsm/L), Stanford solution (409 mOsm/L), and University of Wisconsin solution (315 mOsm/L). Controls had blood perfusion (310 mOsm/L). Postmortem left ventricular pressure-volume curves and myocardial water content were measured. After glutaraldehyde or formalin fixation, dehydration, and paraffin embedding, edema was graded subjectively. RESULTS: Myocardial water content reflected perfusate osmolarity, being lowest in Stanford and University of Wisconsin solutions (p<0.05 versus other groups) and highest in dilute Plegisol (p<0.05). Left ventricular filling volumes were smallest in dilute Plegisol and Plegisol (p<0.05). Osmolarity was not a major determinant of myocardial edema grade, which was highest with University of Wisconsin solution and dilute Plegisol (p<0.05 versus other groups). CONCLUSIONS: Perfusate osmolarity determined myocardial water content and left ventricular filling volume. However, perfusate chemical composition influenced the histologic appearance of edema. Pathologic grading of edema can be influenced by factors other than osmolarity alone.

Attenuation of reperfusion injury with probucol in the heterotopic rat cardiac isograft.

BACKGROUND: We tested the hypothesis that pretreatment with the antioxidant probucol attenuates reperfusion-induced diastolic abnormalities in the heterotopic rat cardiac isograft. METHODS: American Cancer Institute rats (n = 48) were divided into 6 groups. Hearts were arrested by coronary perfusion with 3 ml 4 degrees C University of Wisconsin solution at 60 mmHg. Eighteen donor hearts were divided into 3 groups of 6 and arrested either 1 hour after intraperitoneal injection of 3 ml oil with (Prob Tx) or without (Oil Tx) probucol (300 mg/kg) or without injection (Ctrl Tx). After a 90 minute storage period, abdominal isografting was performed with a total ischemic time of 2 hours. Following 15 minutes of blood reperfusion, donor hearts were rearrested and excised. Recipients' native hearts (NH, n = 18) were also arrested. Two additional groups with (Prob NR, n = 6) and without (Ctrl NR, n = 6) probucol pretreatment were arrested and subjected to 2 hours of ischemia without reperfusion. Postmortem LV pressure-volume curves and myocardial water content (MWC) were measured. RESULTS: At each pressure interval normalized LV volume (LVV) was significantly greater for Prob Tx than Oil Tx or Ctrl Tx. All isograft groups had significantly lower LVV at all pressure intervals and higher MWC than non-transplanted hearts. CONCLUSIONS: Pretreatment with probucol attenuates reperfusion-induced decreases in LVV in the heterotopic rat heart isograft model. Probucol, which is orally active in humans, merits further study for its potential to improve myocardial protection during cardiac surgery.

Pressure volume curves in arrested heterotopic rat heart isografts: role of improved myocardial protection.

BACKGROUND: To minimize decreases in left ventricular (LV) compliance immediately after rat heart transplantation, we tested several different methods of myocardial protection. MATERIALS AND METHODS: Five groups of ACI rat hearts (n = 6 each) were arrested by coronary perfusion with 5 ml of UW (University of Wisconsin), UW-BDM (UW with 2,3-butanedione monoxime), CU (Columbia University), or CU-BDM solution or by LV injection of potassium chloride and Ringer's lactate immersion (KCl/RL). After abdominal isografting and blood reperfusion for 15 min, transplanted hearts (TxH) were arrested and excised. Diastolic LV pressure-volume curves (LVPVCs) were correlated with myocardial water content (MWC). Native hearts (NH) were arrested identically to TxH and maintained at 4 degrees C by immersion. LVPVCs were measured at 15-min intervals for 90 min. RESULTS: In three of four pressure intervals at Time 0, normalized LV volume (LVV) was smaller (P < 0.05, ANOVA) in KCl/RL native hearts than in the four perfusion groups. LVV decreased significantly in NH after 45-75 min; LVV decreased similarly with time in all groups. In TxH, postarrest LVVs were higher with UW-BDM, CU-BDM, and CU than with UW or KCl/RL (P < 0.05, ANOVA). Expressing LVV of TxH as a percentage of NH, UW-BDM, CU, and CU-BDM provided qualitatively better diastolic properties than KCl/RL and UW. CONCLUSIONS: Thus rat LVPVCs can be improved after heart transplantation with alternative strategies of myocardial protection. KCl arrest decreases LV filling volume in this model and should be avoided.

Spontaneous popliteal artery dissection: a case report and review of the literature.

Spontaneous arterial dissection of a peripheral artery involving an extremity is a rare event. We report a case of atraumatic, nonaneurysmal dissection of the popliteal artery that occurred in a 62-year-old man who was admitted with progressive right lower-extremity claudication. Preoperative arteriography was suggestive of arterial dissection, and surgical treatment was undertaken before irreversible ischemia developed. Intraoperatively, a dissection of the popliteal artery was observed, and the patient underwent femoral-popliteal bypass grafting with the ipsilateral, greater saphenous vein and the popliteal artery was ligated distal to the dissection. Spontaneous dissection limited to the popliteal artery has not previously been reported in the literature. Successful management depends on consideration of the diagnosis, particularly when other, more common diseases have been excluded.

Reversal of iatrogenic myocardial edema and related abnormalities of diastolic properties in the pig left ventricle.

OBJECTIVE: This study examines the resolution of iatrogenic edema and related changes in systolic and diastolic properties in the intact pig left ventricle. METHODS: The coronary arteries were perfused for 50 to 60 seconds with diluted blood (hematocrit value 10% +/- 1%, edema group, n = 5) or whole blood (hematocrit value 28% +/- 1%, control group, n = 6) infused into the aortic root during aortic crossclamping in conditioned, anesthetized pigs. After whole blood reperfusion, preload reduction by vena caval occlusion was used to define systolic and diastolic properties at 15-minute intervals. Left ventricular pressure and conductance, aortic flow, and two-dimensional echocardiography were recorded. RESULTS: Left ventricular mass (wall volume) in the edema group increased significantly compared with that in control pigs after crossclamp removal. Mass returned to preperfusion levels after 45 minutes. The ventricular stiffness constant (beta) increased significantly in the edema group versus the control group, returning to baseline by 30 minutes. The diastolic relaxation constant (tau) and base constant (alpha) did not differ between groups. There was no significant change in contractility. CONCLUSION: Increases in left ventricular mass and diastolic stiffness induced by coronary perfusion with hemodiluted blood resolve after 45 minutes of whole blood perfusion in pigs. This study defines physiologic effects of edema in the normal heart while eliminating most common confounding experimental errors.

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.

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.

A novel arresting solution for study of postmortem pressure--volume curves of the rat left ventricle.

OBJECTIVE: We have found diastolic properties of the rat heart extremely sensitive to the method used to induce arrest. Accordingly, we sought to develop a reliable solution for measuring the LV pressure-volume relationship (LVPVR) in the rat. MATERIALS AND METHODS: The study had five phases: (i) K120Na100, consisting of KCl (120 mEq/L) in NaCl (100 mEq/L) diluted with distilled water was developed in preliminary experiments. (ii) ACI rats were arrested with 3 cc of 4 degreesC KCl (n = 6) or K120Na100 (n = 6) infused into the aortic root. The LVPVR was expressed as normalized volume (Vn) at standardized pressures. Myocardial water content (%MWC) was determined. (iii) Six hearts were arrested with K120Na100 and LVPVRs observed over 1 h. (iv) Four hearts were instrumented with sonomicrometry crystals to compare in vivo and postmortem pressure diameter data. (v) The relation between body weight and dry heart weight was determined in 48 animals. RESULTS: In hearts arrested with KCl, mean Vn at pressures of 10, 15, and 20 mmHg (206 +/- 26, 306 +/- 21, and 336 +/- 25 microl, respectively) was significantly reduced vs K120Na100 hearts (345 +/- 11, 407 +/- 12, and 472 +/- 18 microl) (P < 0.05). Mean %MWC changed insignificantly. Vn at 20 mm Hg became significantly smaller vs initial data 60 min after arrest with K120Na100 (P < 0.05, ANOVA). No differences between in vivo and postmortem mean normalized diameter were observed. The correlation coefficient for the relation between body weight and dry heart weight was 0.80. Conclusions. K120Na100 at 4 degreesC reliably preserves LV diastolic properties in the rat heart for 30 min. Normalization of LV volume to body weight is justified.