Christian Punzengruber

Prolonged mechanical systole and increased arterial wave reflections in diastolic dysfunction

Objective: To evaluate whether left ventricular ejection time indexed for heart rate (left ventricular ejection time index (LVETI)) and arterial wave reflections (augmented pressure (AP)) are increased in patients with diastolic dysfunction (DD). Design: Prospective observational study. Setting: University teaching hospital providing primary and tertiary care. Subjects: 235 consecutive patients undergoing left heart catheterisation were categorised as having definite DD, possible DD or no DD (controls) on the basis of their left ventricular end diastolic pressures and N-terminal brain natriuretic peptide concentrations. Main outcome measures: LVETI and AP were prospectively assessed non-invasively by radial applanation tonometry. In addition, all patients underwent comprehensive echocardiography, including tissue Doppler imaging of mitral annulus velocity in early diastole (E′). Results: LVETI was longer in patients with definite DD than in patients with possible DD and in controls (433.6 (SD 17.2), 425.9 (17.9) and 414.3 (13.6) ms, respectively, p < 0.000001). Arterial wave reflections were higher in definite DD than in possible DD and control groups (AP was 19.4 (SD 8.9), 15.2 (8.0) and 10.7 (6.8) mm Hg, respectively, p < 0.000001). In receiver operating characteristic curve analysis, LVETI detected DD as well as echocardiography (E:E′). Area under the curve for LVETI to differentiate patients with definite DD from normal controls was 0.81 (95% CI 0.72 to 0.89, p < 0.0001). In multivariable logistic regression analysis, LVETI added significant independent power to clinical and echocardiographic variables for prediction of DD. Conclusions: Mechanical systole is prolonged and arterial wave reflections are increased in most patients with DD. Rapid non-invasive assessment of these parameters may aid in confirming or excluding DD.

Severe hyperprolactinaemia is associated with decreased insulin binding in vitro and insulin resistance in vivo.

SummaryWe studied insulin receptor binding and carbohydrate metabolism in 10 patients with severe hyperprolactinaemia and compared the findings with those obtained in 20 healthy control subjects. Insulin binding to monocytes and erythrocytes was significantly decreased in the patients with an excess of prolactin. Scatchard analysis of binding data indicated that a decrease in the number of receptors rather than in receptor affinity seems to be the prevailing cause of lowered binding in hyperprolactinaemic patients. Furthermore, patients with severe hyperprolactinaemia demonstrated significantly elevated blood glucose levels following oral or intravenous glucose load despite having significantly increased insulin levels after glucose administration. The infusion of insulin induced a delayed hypoglycaemic effect and a decreased inhibition of endogenous insulin secretion, as indicated by the suppression of C-peptide in the hyperprolactinaemic patients. The present data indicate that severe hyperprolactinaemia is associated with an insulin-resistant state, which seems to be caused, at least in part, by a down-regulation of insulin receptors.

Valvuloplasty with glutaraldehyde-treated autologous pericardium in patients with complex mitral valve pathology.

BACKGROUND Severe mitral regurgitation associated with complex mitral valve disease often precludes successful surgical repair. The feasibility and the results of valvuloplasty with glutaraldehyde-treated autologous pericardium remain largely unknown. METHODS The cases of 63 patients who underwent operation within an 11-year period were studied. A pretreated autologous pericardial patch was used for leaflet extension plasty, for paracommissural plasty, as a substitute for part of the leaflet, and for reimplantation of ruptured papillary muscles to eliminate severe mitral regurgitation. Patients with a severely calcified annulus after en bloc decalcification had straddling endoventricular pericardial patch annuloplasty for reconstruction of the affected atrioventricular groove. Chordal replacement with a strip of pericardium was chosen if no suitable chordae were available. Pericardium-reinforced suture annuloplasty was used in patients with acute endocarditis resistant to medical therapy. Associated valvuloplasty procedures with Carpentier techniques were also employed. RESULTS There were no operative deaths in this series. At a mean follow-up of 61.1 months (range, 4 to 132 months), mitral regurgitation was absent or trivial in 92.1% of patients by echocardiography. Freedom from reoperation was 95.2% at 1 year and 5 years. Thromboembolic events have not been detected. Thirty percent of patients returned to sinus rhythm. Two patients required valve replacement. CONCLUSIONS Our beneficial results indicate that glutaraldehyde-treated autologous pericardium is suitable for valvuloplasty. It provides durable and predictable repair of valves that might otherwise need to be replaced because of the complex mitral valve disease. The technique is reliable, allows further efficacious repair possibilities, and improves postoperative outcomes. Whether it can prevent late deterioration and calcification requires more investigation.

Valve repair in mitral regurgitation complicated by severe annulus calcification

BACKGROUND Valvuloplasty has significant advantages over valve replacement for mitral regurgitation, but the presence of severe calcification of the mitral valve apparatus has been thought to preclude successful valve reconstruction in general. The purpose of this report is to assess the results of valvuloplasty in patients with severe mitral regurgitation having extensive calcification extending from the mitral annulus to underlying myocardium and parts of the papillary muscles. METHODS Thirty-seven adult patients with severe mitral regurgitation and calcification were operated on between April 1990 and January 1998. Twenty-six patients had degenerative disease, 4 had acute bacterial endocarditis, 6 had postrheumatic fever, and 1 patient had Marfans disease. The valve repair comprised of en bloc decalcification with extensive leaflet debridement and reconstruction of the annulus. Autologous pericardium was used in patch-extended endocardial annuloplasty or leaflet repair. Valve competence was retained after correction of regurgitation by sliding atrioplasty, rotation paracommissural sliding plasty, cusp remodeling, or chordal repair. All patients required a prosthetic annuloplasty. RESULTS Follow-up echocardiography at 47 months (range, 3 to 92 months) showed no or only trivial mitral regurgitation in 33 patients; 3 had grade I-II mitral regurgitation and 1 required valve replacement after 3 months. Freedom of reoperation at 1 and 5 years was 94.6%. At last examination, 33 patients were in New York Heart Association functional class I and 3 in class I-II; there has been no mortality and no thromboembolic events. CONCLUSIONS Valvuloplasty can be safely and successfully carried out in patients suffering from regurgitation associated with severe calcification of the mitral apparatus. With encouraging beneficial midterm results, we suggest patients with calcified valves should not be excluded from mitral repair.

Effects of pressure-controlled intermittent coronary sinus occlusion on regional ischemic myocardial function

Pressure-controlled intermittent coronary sinus occlusion has been reported to reduce infarct size in dogs with coronary artery occlusion, possibly because of increased ischemic zone perfusion and washout of toxic metabolites. The influence of this intervention on regional myocardial function was investigated in open and closed chest dogs. In six open chest dogs with severe stenosis of the left anterior descending coronary artery and subsequent total occlusion, a 10 minute application of intermittent coronary sinus occlusion increased ischemic myocardial segment shortening from 5.5 +/- 1.2 to 8.2 +/- 2.6% (NS) and from -0.1 +/- 2.1 to 2.3 +/- 1.2% (NS), respectively. In eight closed chest anesthetized dogs, intermittent coronary sinus occlusion was applied for 2.5 hours between 30 minutes and 3 hours of intravascular balloon occlusion of the proximal left anterior descending coronary artery. Standardized two-dimensional echocardiographic measurements of left ventricular function were performed to derive systolic sectional and segmental fractional area changes in five short-axis cross sections of the left ventricle. Fractional area change in all the severely ischemic segments (less than 5% systolic wall thickening) was -4.0 +/- 4.7% at 30 minutes after occlusion, and increased with subsequent 60 and 150 minutes of treatment to 13.1 +/- 3.3 and 7.0 +/- 3.3%, respectively (p less than 0.05). At the most extensively involved low papillary muscle level of the ventricle, regional ischemic fractional area change was increased by intermittent coronary sinus occlusion between 30 and 180 minutes of coronary occlusion from -0.4 +/- 0.1 to 14.4 +/- 4% (p less than 0.05), whereas a further deterioration was noted in untreated dogs with coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous coronary artery dissection involving the left main stem: assessment by intravascular ultrasound

This case report describes the devastating consequences of spontaneous coronary dissection in a 36 year old female patient who otherwise had a normal coronary arteriogram. Intravascular ultrasound showed coronary artery dissection and intramural haematoma at the left main stem coronary artery. Acute coronary syndrome developed and subsequently surgical revascularisation was performed successfully.

Clinical Evaluation of Pressure-Controlled Intermittent Coronary Sinus Occlusion: Randomized Trial During Coronary Artery Surgery

Pressure-controlled intermittent coronary sinus occlusion (PICSO) was evaluated in a randomized trial in 30 patients undergoing bypass surgery. PICSO was applied for one hour during early reperfusion. Myocardial function was determined from short-axis cross-sectional views of intraoperative two-dimensional echocardiography. Changes of sectional and segmental wall motion during extracorporeal circulation were analyzed. Although sectional wall motion did not change significantly, hypokinetic segments were preserved better in PICSO-treated patients than in controls (-1.3 +/- 2.4 versus -9.1 +/- 2.6 delta% fractional area change; p less than 0.04). Although not significant, the same trend was found for normal and severely hypokinetic segments. Cumulative enzyme release was related to coronary sinus occluded pressure (r = 0.94; p less than 0.006), indicating washout of metabolites during PICSO. Three months after operation, functional classification was similarly favorable in both groups. Long-term effects of PICSO cannot be predicted because PICSO was applied only during early reperfusion. We conclude that PICSO is a safe procedure and that its short-term beneficial effects on myocardial function suggest a preservation of myocardial viability.

Mechanism of calcium‐independent phosphorylation of sarcoplasmic reticulum ATPase by orthophosphate

Magnesium affects several reaction steps of the calcium transport cycle in sarcoplasmic reticulum membranes [ 1,2]. Recent studies on the effect of magnesium on sarcoplasmic reticulum function [3] indicate a dual role of magnesium on the phosphorylation of sarcoplasmic reticulum transport ATPase from ATP, as evaluated from analysis of the exchange rate of y-phosphate between ATP and ADP [4] in the presence of saturating calcium concentrations: (i) That magnesium activates the enzyme directly; (ii) That it represents part of the substrate MgATP for the phosphorylation reaction [3]. From studies on the role of magnesium in calciumindependent and calciumdependent phosphorylation of sarcoplasmic reticulum transport ATPase from orthophosphate [5-191, the formation of a magnesium-phosphoprotein in calcium-independent phosphorylation was suggested [ 181. Based on the good fit of a reaction scheme to the data the following features were proposed: (i) The phosphoprotein (Mge E-P,), in which the phosphate is covalently bound to the enzyme, is in equilibrium with the Michaelis complex (Mg . E . Pi), the concentration of which is determined by the concentration of free orthophosphate and free magnesium; (ii) The binding of orthophosphate and magnesium appears to be interdependent, both ligands apparently bind randomly [ 181.

Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation.

BACKGROUND Accurate prediction of survival to hospital discharge in patients who achieve return of spontaneous circulation after cardiopulmonary resuscitation (CPR) has significant ethical and socioeconomic implications. We investigated the prognostic performance of serum neuron-specific enolase (NSE), a biochemical marker of ischemic brain injury, after successful CPR. METHODS In-hospital or out-of-hospital patients with nontraumatic normothermic cardiac arrest who achieved return of spontaneous circulation (ROSC) following at least 5 minutes of CPR were eligible. Neuron-specific enolase levels were assessed immediately, 6 hours, 12 hours and 2 days after ROSC. Subjects were followed to death or hospital discharge. RESULTS Seventeen patients (7 men, 10 women) were enrolled during a 1-year period. Median (range) NSE levels in survivors and non-survivors respectively were as follows: immediately after ROSC: 14.0 microg/L (9.1-51.4 microg/L) versus 25.9 microg/L (10.2-57.5 microg/L); 6 hours after ROSC: 15.2 microg/L (9.7-30.8 microg/L) versus 25.6 microg/L (12.7-38.2 microg/L); 12 hours after ROSC: 14.0 microg/L (8.6-32.4 microg/L) versus 28.5 microg/L (11.0-50.7 microg/L); and 48 hours after ROSC: 13.1 microg/L (7.8-29.5 microg/L) versus 52.0 microg/L (29.1-254.0 microg/L). Non-survivors had significantly higher NSE levels 48 hours after ROSC than surivors (p = 0.04) and showed a trend toward higher values during the entire time course following ROSC. An NSE concentration of >30 microg/L 48 hours after ROSC predicted death with a high specificity (100%: 95% confidence interval [CI] 85%-100%), and a level of 29 microg/L or less at 48 hours predicted survival with a high specificity (100%: 95% CI 83%-100%). CONCLUSIONS Serum NSE levels may have clinical utility for the prediction of survival to hospital discharge in patients after ROSC following CPR over 5 minutes in duration. This study is small, and our results are limited by wide confidence intervals. Further research on ability of NSE to facilitate prediction and clinical decision-making after cardiac arrest is warranted.

Bicyclo-prostaglandin E2 metabolite in congestive heart failure and relation to vasoconstrictor neurohumoral principles

Vasodilator prostaglandins may play a role in maintaining circulatory homeostasis in patients with congestive heart failure (CHF). Plasma levels of bicyclo-prostaglandin E2 metabolite (PGEm), a chemically stabilized degradation product of the vasodilator prostaglandin E2, were determined in 45 patients with chronic CHF (New York Heart Association class II, III or IV). Mean circulating levels of bicyclo-PGEm were significantly elevated in patients with functional class III (72 +/- 8 pg/ml) or IV CHF (77 +/- 10 pg/ml) compared with control subjects (49 +/- 3 pg/ml) and patients with functional class II CHF (49 +/- 4 pg/ml). Bicyclo-PGEm concentrations correlated with plasma renin activity (r = 0.68, p less than 0.001) and plasma angiotensin II (r = 0.56, p less than 0.001) and plasma noradrenalin levels (r = 0.34, p less than 0.05). An inverse correlation was found between serum sodium concentrations and levels of bicyclo-PGEm (r = 0.46, p less than 0.01) as well as plasma renin activity (r = 0.66, p less than 0.001). Thus, prostaglandin E2 levels in plasma are increased in patients with severe CHF.