Atrial fibrillation in father and son after ingestion of cold substances.

A man and his father each developed atrial fibrillation after the ingestion of a frozen sweet. In the son, atrial fibrillation recurred with the subsequent ingestion of cold beverages. Neither patient had documented episodes of atrial fibrillation at any other time. The son also had multiple other episodes of palpitation, suggesting brief episodes of atrial fibrillation, and these occurred only with the ingestion of cold substances. Possible mechanisms include direct cooling of the left atrium through the wall of the esophagus and autonomic stimulation by the cold substance.

Aortic dissection and patent ductus arteriosus in three generations.

Aortic dissection was found in a woman, her 2 sons, and 1 of her 3 daughters, and the 3 affected children and a granddaughter had patent ductus arteriosus. The pattern of inheritance of this unique syndrome probably is an autosomal dominant one.

Dyspnea in a woman infected with the human immunodeficiency virus.

Shortness of breath is a common complaint encountered in both the ambulatory and acute care setting. In patients infected with the human immunodeficiency virus, dyspnea often heralds the onset of a potentially life-threatening opportunistic infection. We present a case of a rare cause of dyspnea in the general population and to our knowledge the first such case reported in the setting of human immunodeficiency virus infection in the United States.

Congenital bilateral pulmonary venous stenosis in an adult:: diagnosis by Echo-Doppler.

A 22-year-old man with life-long exertional fatigue and dyspnea was diagnosed as having bilateral congenital pulmonary venous stenosis by echocardiography with color Doppler examination. Fibrous membranes overlying the entrances of the veins to left atrium were the cause of obstruction and were easily resected.

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes.

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V1 to V3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V1 to V3 (P = 0.04). However, in the entire population, there was a highly significant correlation (P = .003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes.

Serial echocardiographic and clinical evaluation of valvular regurgitation before, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine.

OBJECTIVE: The prevalence of cardiac valvular regurgitation demonstrated by echocardiography in patients who took appetite-suppressant medication for weight loss has been assessed at 5%-30%. We studied 86 patients who had echocardiograms before treatment with appetite suppressants to determine the incidence of new cases and to evaluate the clinical implication of the echocardiographic findings. RESEARCH METHODS AND PROCEDURES: We studied 69 men [Mean+/-Standard Deviation (S) age 49+/-8] and 17 women (mean+/-S age 50+/-7) who had 233 echocardiograms before, during, and after a weight-loss program that used predominantly fenfluramine (or dexfenfluramine) with mazindol (or phentermine). Mean drug exposure was 17 months. Blinded echocardiographic readings were performed to identify and grade aortic regurgitation (AR) or mitral regurgitation (MR). RESULTS: Seven of 86 patients (8%) had pre-existing regurgitation with five (6%) meeting our case definition. Thirteen (16.5%) of initially normal patients developed valvular regurgitation and were new cases. Of the new cases, 12 were grade I/IV AR and one was both grade II/III MR and II/IV AR. All 13 patients were asymptomatic, and only two aortic insufficiency murmurs could be auscultated. There was significantly greater risk for developing valvulopathy for those who took medications longer than 6 months (p = 0.03), and no new cases were observed in patients exposed for less than 8 months. No increased risk associated with age, presence of hypertension, or exposure to fenfluramine-phentermine combination was demonstrated. Although there was a higher incidence of new regurgitation in women (31% vs. 13% for men), this was not statistically significant (p = 0.093). DISCUSSION: Some patients who had normal echocardiograms at baseline developed cardiac valvular regurgitation after exposure to fenfluramine or dexfenfluramine with mazindol or phentermine. The development of valvulopathy was significantly correlated with duration of exposure. The clinical implications of echocardiographically demonstrated regurgitation are uncertain, since there were only two audible murmurs and no other clinically relevant signs or symptoms among the patients.

Effect of hypoxia and hypoxia/reoxygenation on proteoglycan metabolism by vascular smooth muscle cells.

Hypoxia and hypoxia/reoxygenation are known to affect vascular smooth muscle cell physiology. In this study, we first investigated proteoglycan synthesis by human aortic smooth muscle cells exposed to normoxia, hypoxia, or hypoxia/reoxygenation. We then compared the newly synthesized proteoglycans from normoxic and hypoxic-reoxygenation cultures for their ability to bind low density lipoprotein (LDL). Confluent smooth muscle cells under normoxia, hypoxia, or hypoxia/reoxygenation were pulsed with [35S]sulfate, and secreted and cell-associated proteoglycans were analyzed. Secreted proteoglycans in cultures exposed to hypoxia (4 h)/reoxygenation (19 h) increased 28% over those of cells continuously exposed to normoxia. Cell-associated proteoglycans did not differ significantly between the two groups. In contrast, hypoxia (4 h) followed by a 30-min reoxygenation produced a 37% decrease in newly synthesized proteoglycans. Hypoxia alone also resulted in a 24% decrease in secreted proteoglycans and a 20% decrease in cell-associated proteoglycans. Proteoglycans newly synthesized by smooth muscle cells exposed to normoxia and hypoxia/reoxygenation did not differ in their charge densities and molecular size but did differ in glycosaminoglycan composition. Exposure of smooth muscle cells to hypoxia/reoxygenation produced a 60% increase in a proteoglycan subfraction that bound LDL with very high affinity. The incorporation of [3H]leucine into total cellular protein decreased significantly following exposure of smooth muscle cells to hypoxia as well as hypoxia/reoxygenation. These results indicate that hypoxia and hypoxia/reoxygenation cause major alterations in proteoglycan metabolism by vascular smooth muscle cells.

Cardiac surgery for grown-up congenital heart patients: survey of 307 consecutive operations from 1991 to 1994.

The cardiac surgery performed from 1991 to 1994 in a unit dedicated specifically for grown-up congenital heart (GUCH) patients was reviewed to determine the frequency of various procedures, incidence of first and reoperations, early mortality, and its determinants. The 295 patients, aged 16 to 77 years (31 +/- 13), had 307 operations. First operations (n = 128, 42%) were most commonly for closure of atrial septal defect (n = 40), aortic valve replacement (n = 31) or repair of aortic coarctation (n = 14). Reoperations were more frequent (n = 179, 58%) and divided among first corrective repair (n = 49), reoperation after corrective repair (n = 115), and further palliation (n = 15). First corrective surgery was mainly for aortic valve disease (n = 17), Fallot (n = 7), and lesions needing a Fontan procedure (n = 5). Reoperations after corrective repair were needed for aortic valve disease (n = 43), right-sided conduit (n = 30), or recoarctation (n = 11). Early mortality was influenced by presence of central cyanosis (9 of 49, 18% in cyanotic patients; 12 of 258, 5% in acyanotic; p <0.001), increased number of previous operations (0 = 4%, 1 = 7%, 2 = 11%, >2 = 13%; p = 0.003), and increasing age of patients. Cyanotic patients had more serious postoperative complications: pleural and pericardial effusions, severe bleeding, renal insufficiency, and sepsis, and their hospital stay was longer compared with acyanotic patients (20 +/- 17 vs 11 +/- 8 days; p <0.001). In GUCH patients, reoperations cause the largest demand on cardiac surgical services. Increased survival of patients with complex cardiovascular malformations brings difficult challenges not only to cardiologists but also to cardiovascular surgeons. There is a need to provide continued highly specialized care. Resources, patients, and funding should be concentrated in a few designated centers.

Value of leads V7-V9 in diagnosing posterior wall acute myocardial infarction and other causes of tall R waves in V1-V2.

Left posterolateral chest leads (V7, V8, V9) helped distinguish the multiple causes of tall R waves in V1 and/or V2, diagnosed true posterior myocardial infarction when standard leads did not, and identified the presence or absence of posterior injury in patients with inferior infarction.

Enhanced synthesis of proteoglycans by vascular endothelial cells treated with phorbol ester.

We investigated the biosynthesis of proteoglycans (PG) in endothelial cells following their treatment with phorbol 12-myristate 13-acetate (PMA). Confluent cultures of bovine aortic endothelial cells were incubated in the presence and absence of PMA (100 ng/ml) and then pulsed with [35S]sulfate, [3H]glucosamine, or [35S]sulfate plus [3H]leucine for varying times in the absence of PMA. Alternatively, confluent endothelial cells were simultaneously incubated with PMA and [35S]sulfate for varying times. The metabolically labeled PG in the cell layer and medium were analyzed. Both short-term and prolonged exposure of endothelial cells to PMA significantly stimulated PG synthesis, regardless of the experimental conditions. [35S]sulfate incorporation into newly synthesized PG in PMA-treated cells also increased by 1.7-fold and 3.6-fold over control cells, following a 15-min and 30-min pulse, respectively. Cycloheximide markedly inhibited the increased synthesis of PG in PMA-treated cells, while actinomycin D produced a moderate inhibition. PG secretion was increased in PMA-treated cells compared with control cells, while there was no significant difference in PG degradation between the two cultures. PG from control and PMA-treated endothelial cell cultures did not differ in composition or hydrodynamic sizes. The incorporation of [3H]leucine into total cellular proteins decreased significantly following exposure of endothelial cells to PMA. Endothelial cells exposed to PMA for 3 h had significantly more protein kinase C (PKC) activity than did control cells. Inhibition of PKC by calphostin C abolished the PMA-mediated stimulation of PG synthesis in endothelial cells. The results indicate that PMA stimulates PG synthesis in endothelial cells either directly or indirectly through a PKC dependent mechanism.

Elevated expression of proteoglycans in proliferating vascular smooth muscle cells.

Smooth muscle cell (SMC) proliferation and increased production of arterial wall proteoglycans (PG) are implicated in atherogenesis. We investigated the effect of SMC proliferation on the biosynthesis of PG and the ability of the newly synthesized PG to bind low density lipoprotein (LDL). Proliferating and quiescent human aortic SMC were pulsed with [35S]sulfate for 24 h. Secreted and cell-associated PG were then analyzed. When SMC plated at a low density were induced to proliferate, PG synthesis increased significantly in comparison with quiescent cells. This was the net result of a 2.7-fold increase in secreted PG and a 1.3-fold increase in cell-associated PG. The increased PG synthesis in proliferating SMC correlated with a significant increase in the steady-state level of mRNA for perlecan and biglycan, and a modest increase in the versican-specific mRNA. The mRNA for decorin showed a 40% decrease. The increased PG secretion in proliferating cultures was due to increases in heparan sulfate PG, dermatan sulfate PG, and chondroitin sulfate PG secretion. Quiescent SMC at confluency produced 50% less PG than the corresponding SMC plated at a low density. Although confluent SMC stimulated to proliferate also had increased PG synthesis, this was 50% less than the PG synthesis by proliferating SMC that were initially plated at a low density. The PG synthesized by proliferating and quiescent SMC did not differ in charge density and molecular size. Secreted PG from both quiescent and proliferating cultures contained subfractions that bound LDL with high affinity. However, compared with quiescent cultures, the proliferating cultures produced more of a PG subfraction that exhibited very high affinity to LDL (31.6% in quiescent cultures versus 40.8% in proliferating cultures). These results indicate that PG metabolism is altered significantly in proliferating human SMC which might have implications in the pathophysiology of atherosclerosis.

Isolation and characterization of a proteoglycan variant from human aorta exhibiting a marked affinity for low density lipoprotein and demonstration of its enhanced expression in atherosclerotic plaques.

Proteoglycans (PG) are implicated in the pathophysiology of atherosclerosis due to their ability to complex with plasma low density lipoproteins (LDL). Studies were conducted to determine whether human aorta contains PG subclasses that exhibit enhanced LDL binding ability. PG were isolated from normal and atherosclerotic aortas by a combination of dissociative extraction and ion-exchange chromatography. The PG were further subfractionated on an LDL affinity column based on their binding affinity to LDL. Two PG fractions exhibiting high-affinity binding to LDL, as evidenced by their elution at 1.0 and 1.5 M NaCl, respectively, were isolated from both normal and atherosclerotic tissue. Compared with normal tissue, atherosclerotic tissue showed a twofold increase in the high-affinity PG that eluted at 1.5 M NaCl. Gel filtration of the high-affinity PG from normal tissue yielded two peaks (nPG2 and nPG3), while the high-affinity PG from plaque tissue was resolved into three peaks (pPG1, pPG2, and pPG3). pPG1 eluted at the void volume of the column, indicating that it was of very large molecular size. The hydrodynamic size of pPG2 was larger than that of the corresponding nPG2 (Kav = 0.44 versus 0.51), while pPG3 had the same hydrodynamic size as nPG3 (Kav = 0.86). The high-affinity PG subfractions from normal aorta contained varying proportions of chondroitin sulfates, dermatan sulfates, and heparan sulfate. In contrast, the PG subfractions from plaque tissue contained predominantly chondroitin sulfates and heparan sulfate. In vitro complexes of LDL and the high-affinity PG fractions from normal aorta and plaque tissue stimulated cholesteryl ester synthesis in human monocyte-derived macrophages. However, the LDL-plaque PG complex was significantly more potent than the LDL-normal aorta PG complex in this respect. These results indicate that PG subclasses with enhanced binding affinity to LDL occur in the normal human aorta and that their concentration increases significantly in atherosclerotic lesions. In addition, the high-affinity PG in plaque tissue have altered characteristics and increased ability to stimulate LDL-mediated cholesterol ester synthesis in macrophages. This could lead to increased lipid deposition during atherogenesis.