In vitro coronary artery imaging with sixteen-slice helical computed tomography.

PURPOSE: To determine the benefits of submillimeter coronary computed tomography (CT) angiography in vitro. MATERIAL AND METHODS: The coronary arteries of three domestic pigs were filled with contrast agent and depicted with clinically applicable CT angiography protocols with a slice thickness of 0.63 to 2.5 mm. RESULTS: With 2.5 mm slices, only the third-degree coronary artery branches could be discerned. With 1.25 mm slices, some fourth-degree branches of the right coronary artery could be discerned upon maximum intensity projections. With 0.63mm slices, fourth-degree coronary artery branches could be discerned in all locations. CONCLUSION: The introduction of 16-row detector CT with submillimeter z-axis resolution translates into an order-of-magnitude benefit for the depiction of coronary artery branches.

Adenovirus-mediated overexpression and stimulation of the human angiotensin II type 2 receptor in porcine cardiac fibroblasts does not modulate proliferation, collagen I mRNA expression and ERK1/ERK2 activity, but inhibits protein tyrosine phosphatases.

The contribution of the angiotensin (Ang) II type 2 receptor (AT2R) to cardiac hypertrophy is still controversial. Here we examined the effect of overexpressing the human AT2R in cultured porcine cardiac fibroblasts (pFib) on proliferation, procollagen I mRNA expression, and - as putatively underlying signal-transduction pathways - on mitogen-activated protein kinase ERK1/ERK2 and phosphotyrosine phosphatase activities. As quantitated by 125I-(Sar1,Ile8)-Ang II binding, transduction of cardiac fibroblasts with the adenoviral AT2R expression vector led to a six- to tenfold higher AT2 than endogenous Ang II type 1 receptor (AT1R) expression. The overexpressed AT2R had the same apparent molecular mass as the endogenous AT2R in rat PC12W cells. Proliferation was not significantly lower in AT2R expressing pFib than in antisense-transduced controls (TA2) upon stimulation with Ang II (AT2R 110.5+/-4.8% vs. TA2 110.2+/-5.5%), Ang II plus the AT1R blocker Irbesartan (97.1+/-1.4% vs. 108.0+/-5.0; P=0.052) and the partial AT2R antagonist CGP42112 at the agonistic concentration of 50 nM (92.1+/-2.7% vs. 99.8+/-3.1%; P=0.053). Procollagen Ialpha2 (COL1A2) mRNA levels were quantitated by (a) northern blot analysis and (b) reverse transcriptase polymerase chain reaction. COL1A2/GAPDH (a) and COL1A2/beta-actin (b) ratios revealed no differences between AT2R-transduced fibroblasts and antisense controls when stimulated with Ang II (1 microM, 24 h) plus Irbesartan and 10 ng/ml transforming growth factor beta1. Ang II stimulation of the endogenous AT1R increased extracellular signal regulated kinase 1/2 activities. This response was reduced by Irbesartan, but PD123319 had no effect. Time course and magnitude of Ang II stimulated ERK1/ERK2 activation was identical in AT2R-transduced and control cells. Also, neither simultaneous nor Ang II pre-stimulation, suggested to induce gene expression of the MAP kinase phosphatase 1, modulated phorbol myristate acetate-stimulated ERK1/ERK2 activation in AT2R-transduced pFib, in AT2R-transduced human umbilical vein endothelial cells, and in PC12W cells. By the use of a tyrosine phosphatase assay we observed an inhibition of phosphotyrosine phosphatase activity by 30.8% (P=0.009, n=5) after 5 min Ang II stimulation of AT2R-expressing pFib. Immunoprecipitation-tyrosine phosphatase assays revealed that inhibition of phosphotyrosine phosphatase 1B, which regulates insulin signaling, contributed to this effect. In conclusion, stimulation of the overexpressed human AT2R in porcine cardiac fibroblasts inhibited tyrosine phosphatase activity but had no significant effect on fibroblast functions related to cardiac fibrosis. It is conceivable that possible antifibrotic AT2R effects are species specific and/or require the interaction between fibroblasts and cardiomyocytes, probably via paracrine factors, or mechanical load.

Continuous measurements of renal perfusion in pigs by means of intravascular Doppler.

BACKGROUND: Changes in renal blood flow are considered to play a significant role in the induction and maintenance of kidney failure, but are difficult to monitor with currently available techniques. The objective was to validate renal flow measurements with Doppler guidewires and to apply this technique to assess dose and time dependency of the renal vascular effects of norepinephrine (NE). METHODS: In 10 anesthetized pigs, flow velocity in renal arteries (FVart) and veins (FVvein) and volumetric renal blood flow (VBF) were measured before and after intravenous bolus application of incremental doses of NE (2 to 200 microg). RESULTS: FVart curves exactly reflected the changes in VBF. Beat-to-beat analysis revealed a strong linear correlation over a mean VBF range of less than 0.05 to 0.35 L/min (median correlation coefficient with FVart, r = 0.998), and significant but less close relationships were also found between VBF and FVvein. Ten seconds after the administration of 200 microg NE, FVart dropped from 71 to 6 cm/sec and was 90% reversible after 48 seconds. Similarly, the renal vascular resistance temporarily rose from 988 to 13711 mm Hg. min/L. In contrast, NE-induced increases in systemic vascular resistance were on average a maximum of 1.5-fold but persisted for more than 60 seconds. CONCLUSIONS: Doppler flow measurements in the renal artery provide an excellent surrogate of volumetric blood flow, which may be useful for continuous monitoring of renal hemodynamics. The renal vasculature is more sensitive when compared with the systemic vasculature, but also appears to evoke more efficient counter-regulatory mechanisms in response to NE.

Valve selection and choice in surgery of endocarditis.

The experience of the German Heart Center with valve selection and choice of size of prostheses for aortic root endocarditis is hereby reported. This experience includes 37 cases of aortic root endocarditis between 1986 and 1989. Mechanical, bioprosthetic, and homograft valves were used depending on the size, annular pathology, and general conditions related to the patient's medical history. Operative techniques are presented. Regardless of the type of valve replacement device, extensive annular destruction indicates a difficult and complex operation with long-term early and late results inferior to those in patients without annular abscess.

[Carnitine metabolism--changes in the end stage of dilated cardiomyopathy and ischemic heart muscle disease]. / Carnitinstoffwechsel--Veränderungen im Endstadium der dilatativen Kardiomyopathie und der ischämischen Herzmuskelerkrankung.

Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)

[Recurring pulmonary artery embolisms and disseminated intravascular coagulation in right atrial myxoma]. / Rezidivierende Lungenarterienembolien und Verbrauchskoagulopathie bei rechtsatrialem Myxom.

A 33 year old woman presented with dyspnea and dizziness. These symptoms had recurred several times during the months preceding. At initial investigation we palpated a tumor in the upper abdomen corresponding to the sonographic finding of a 10 X 10 cm sized cystic tumor in the liver. Because of reduction of fibrinogen, prolonged thrombin time and thrombocytopenia a malignant disease involving the liver and producing pulmonary embolism and disseminated intravascular coagulation was suspected. However, during routine echocardiography a right atrial mass prolapsing in the right ventricle was detected. After normalization of fibrinogen and thrombin-time following a low dose heparin therapy a myxoma sized 6 X 5 cm was removed from the right atrium. The patient did not recover and died 20 days following surgery. At autopsy the liver tumor proved to be a benign cholangioendothelial cyst.

Short-term hemodynamic results after right ventricular outflow tract reconstruction using a cusp-bearing transannular patch.

Correction of right ventricular outflow tract obstruction remains a challenge to cardiovascular surgeons. In order to relieve this obstruction and at the same time prevent or minimize pulmonary insufficiency, we inserted a cusp-bearing transannular patch (monocusp) in 14 patients. To test this objective, we restudied 13 of these patients 0.5 to 4 months postoperatively, including quantifying pulmonary insufficiency using an accurate videodensitometric method. In all patients a degree of pulmonary insufficiency ranging from 8% to 46% of total stroke volume (mean 22.7 +/- 10.6%) was measured, and in all but one a residual right ventricular outflow pressure gradient of 2 to 22 mm Hg (mean 10 +/- 7 mm Hg) was measured. There was an inverse relation between the degree of pulmonary insufficiency and both the pressure gradient (r = -0.89) and the ratio of the pulmonary valve ring diameter to monocusp depth (r = -0.67). An ideal reconstruction of the right ventricular outflow tract obstruction, without any postoperative pulmonary insufficiency and stenosis, was not achieved by the implantation of a monocusp in the described fashion. The postoperative results were acceptable in only a few patients. A reduction of pulmonary insufficiency seems to be associated with a small residual pressure gradient as well as a relatively small cusp size. Additional studies are necessary to further improve surgical correction of right ventricular outflow tract obstruction with reproducible and predictable results.