Post-sternotomy internal mammary arteriovenous fistula.

Arteriovenous fistula from the mammary artery is a rare complication following cardiac surgery. The fistula usually develops within the first 2 weeks after surgery and is initially asymptomatic. Typically, a continuous machinery murmur is heard along the parasternal border of the chest wall. A patient with an arteriovenous fistula between the right internal mammary artery and mammary vein following a combined aortic valve and coronary bypass operation is described. A transthoracic colour Doppler scan led to the diagnosis of the fistula. Because of potential late complications endovascular embolisation of the fistula was successfully performed.

Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells.

The current model of the arterial response to injury suggests that proliferation of vascular smooth muscle cells is a central event. Mitogen activated protein kinases are part of the final common pathway of intracellular signalling involved in cell division and thus constitute an attractive target in attempting to inhibit this proliferation. We hypothesised that antisense oligonucleotides to mitogen activated protein kinase would inhibit serum induced smooth muscle cell proliferation by downregulating the protein. Porcine vascular smooth muscle cells were cultured and an antisense oligonucleotide sequence against the ERK family of mitogen activated protein kinases (AMK1) was introduced by liposomal transfection. Sense oligonucleotides and a random sequence were used as controls. Proliferation was inhibited by AMK1 versus the sense controls, as assessed by tritiated thymidine incorporation (P<0.01). Immunoblots revealed downregulation of the target protein by AMK1 by 63% versus the sense control (P<0.05). In conclusion, antisense oligonucleotides specifically inhibited proliferation and downregulated the target protein. This is consistent with a central role for mitogen activated protein kinases in vascular smooth muscle cell proliferation in the porcine model. In addition, the data suggest a possible role for antisense oligonucleotides in the modulation of the arterial injury response.

The physiological role of endogenous endothelin in the regulation of human coronary vasomotor tone.

OBJECTIVES: The study was done to investigate the physiological role of endogenous endothelin-1 in the human coronary circulation by studying the effect of an intracoronary infusion of the specific endothelin receptor subtype A (ETA) receptor antagonist BQ123 on coronary vasomotor tone. BACKGROUND: Endothelin-1 contributes to the maintenance of peripheral vascular tone in humans. However, its physiological role in the human coronary vasculature is unknown. METHODS: We studied 12 patients (mean age 54.7 +/- 2.5 years, 3 men) undergoing cardiac catheterization for investigation of atypical chest pain, with angiographically normal coronary arteries. Coronary artery cross-sectional area was measured with digital quantitative coronary angiography, and coronary blood flow was assessed with an intracoronary Doppler flow wire. Flow-mediated (adenosine, 18 microg) and agonist-mediated (substance P, 20 pmol/min for 2 min) endothelial responses were measured prior to study. BQ123 (40 nmol/min for 15 min and monitored for a further 15 min) was infused into the left coronary artery. RESULTS: The BQ123 caused significant dilation of the proximal (artery cross-sectional area: 8.08 +/- 0.9 to 8.88 +/- 0.9 mm2; p < 0.05), mid (5.32 +/- 0.8 to 6.49 +/- 0.8 mm2; p < 0.001) and distal study vessel (2.11 +/- 0.2 to 2.50 +/- 0.2 mm2; p < 0.05). There was an increase in coronary blood flow (26.8 +/- 2.8 to 32.8 +/- 3.4 ml/min; p < 0.001) but no change in systemic hemodynamics. Baseline flow- or substance P-induced epicardial vasodilation did not correlate with the degree of vasodilation induced by BQ123. CONCLUSIONS: These data uncover a role of endogenous endothelin-1 in the maintenance of basal vasomotor tone in patients with angiographically normal coronary arteries.

Stent implantation reduces restenosis in patients with suboptimal results following coronary angioplasty.

BACKGROUND: Primary intracoronary stenting reduces the rate of restenosis when compared with balloon angioplasty (PTCA) in selected patients. The strategy of PTCA followed by provisional stent placement for suboptimal PTCA results may be preferable to universal stenting but has not yet been tested in a randomized trial. METHODS: An attempt was made to obtain an optimal result with PTCA alone in 143 patients. Stenting was required in 50 patients (35%) for significant coronary dissection or PTCA failure. In the remaining 93 patients, the angiographic result was assessed immediately using on-line quantitative coronary angiography and classified as either optimal (<15% residual stenosis) or suboptimal (>/=15% residual stenosis). Sixteen patients (11%) had an optimal result from PTCA. The remaining 77 (54%) patients had a suboptimal result and were immediately randomized either to no further treatment or to the placement of a stent. The primary end-point was the rate of restenosis (>50% stenosis), assessed by quantitative coronary angiography, at 6 months. RESULTS: Angiographic follow-up was completed in 132 patients. Restenosis occurred in 53 (36,69)% of patients with a suboptimal result randomized to PTCA alone compared with 24 (12,41)% of patients randomized to stent (P=0.023). There was no significant difference in minimal luminal diameter at follow-up between the randomized groups. The rate of restenosis was 14 (2,43)% in patients with an optimal PTCA result and 14 (5,28)% in those that required stenting. CONCLUSIONS: Optimal angiographic results following conventional PTCA are rare and the restenosis rate following suboptimal results is high. The strategy of stenting suboptimal results is associated with a significant reduction in the rate of stenosis.

Reciprocal changes in endothelial and inducible nitric oxide synthase expression following carotid angioplasty in the pig.

OBJECTIVE: Nitric oxide produced by nitric oxide synthase appears to have an important role in the regulation of arterial tone, platelet adhesion and smooth muscle cell proliferation. Our aim was to investigate the effects of balloon angioplasty on expression of endothelial NO synthase (cNOS) and inducible NO/synthase (iNOS) in the pig carotid artery and to relate any changes in expression to the processes of reendothelialisation and vascular repair. METHODS: Pigs were sacrificed at various time points to follow NOS expression in the neointima, media and regenerated endothelium. Immunocytochemical staining was used to localize cNOS and iNOS expression in the vessel wall. Relative amounts of cNOS were measured using quantitative in vitro alitoradiography. cNOS mRNA and iNOS mRNA was quantified by competitive PCR based on the sequenced cDNA of porcine cNOS and iNOS. RESULTS: Uninjured carotid arteries exhibited dense uniform luminal endothelial staining for cNOS. Balloon angioplasty caused denudation of cNOS immunoreactive cells and a marked reduction of cNOS gene expression but a complete recovery was noted by day 35. In normal uninjured carotid arteries no evidence of iNOS immunoreactivity was demonstrable but 24 h after injury, marked homogeneous iNOS immunoreactivity was detected in medial vascular smooth muscle cells. By 5 days, staining was evident in cells within the forming neointimal layer with no evidence of iNOS immunoreactivity in the media. iNOS immunoreactivity persisted in cells at the luminal surface at 7 days and iNOS gene expression appeared to be sustained in some animals with ruptured internal elastic lamina at 21 days. CONCLUSION: Balloon injury is associated with de-endothelialisation and a marked reduction in cNOS gene expression and activity. iNOS is induced throughout the arterial media within VSMC soon after balloon injury and persists for up to 21 days. These observations imply an important regulatory role for locally generated NO in the pathophysiological response to balloon injury.

Local delivery of platelets with encapsulated iloprost to balloon injured pig carotid arteries: effect on platelet deposition and neointima formation.

Local delivery of a drug to the arterial wall during angioplasty is an approach which might reduce the incidence of occlusive events such as thrombosis and restenosis, without the risk of systemic side effects. By exploiting their natural primary haemostatic properties, platelets, with encapsulated drugs, can be targeted to a vessel wall injury site and act as a depot for sustained release. The platelet plasma membrane can be reversibly permeabilised by high voltage, short duration electrical pulses (electroporation). Drugs will diffuse into porated platelets and become trapped on resealing. We have studied the effects of autologous platelets, electroloaded with the stable prostacyclin analogue, iloprost on platelet deposition and neointima formation in a pig carotid angioplasty model. Iloprost loaded or control platelets were delivered locally and immediately to the balloon injured site using a double balloon delivery catheter. Acute platelet deposition was measured using 111-Indium, and neointima formation at 21 days post angioplasty was assessed by morphometric analysis. In pigs treated with iloprost loaded platelets, platelet deposition on the artery at 2 hours post injury was dramatically reduced (to approximately monolayer coverage), when compared with arteries from pigs treated with control platelets. In pigs with deeply injured arteries, i.e. with extensively ruptured internal elastic lamina (IEL), platelet deposition was reduced by 88% compared with control arteries (118 +/- 20 x 10(6)/cm vs. 14 +/- 2 x 10(6)/cm, means +/- SI, 2P < 0.001). In minimally injured arteries (IEL intact) a 65% reduction in platelet deposition was observed (55 +/- 24 x 10(6)/cm vs. 19 +/- 3 x 10(6)/cm. 2P < 0.002). A high concentration of free iloprost, delivered to the angioplasty site, with control platelets, had far less effect on platelet deposition, substantiating the advantage of platelet encapsulation. At 21 days post injury, morphometry of the carotid arteries after treatment with iloprost loaded platelets showed significant reductions in intimal area and intimal/medial ratios in minimally injured vessels (P < 0.05) as compared with vessels from pigs treated with control platelets. With deeply injured vessels, the mean differences (control vs. treated) for the same morphometric parameters were not significant. This novel approach of electro-encapsulating drugs within autologous platelets, and using them as highly biocompatible and biodegradable drug targeting vehicles might, with the appropriate choice of encapsulated agent, have potential for reducing the incidence of occlusion after angioplasty and thrombolysis procedures.

Upregulation of basement membrane-degrading metalloproteinase secretion after balloon injury of pig carotid arteries.

Basement membrane-degrading metalloproteinases (gelatinases) appear necessary for vascular smooth muscle cell migration and proliferation in culture and for intimal migration of cells after balloon injury to the rat carotid artery. We investigated in the present study the secretion of gelatinases from pig carotid artery tissue after balloon injury. Segments of injured artery and segments proximal and distal to the area of injury were removed 3, 7, and 21 days after balloon dilatation. Medial explants from these segments were then cultured for 3 days, and the serum-free conditioned media were subjected to gelatin zymography. Production of 72- and 95-kD gelatinases was quantified by densitometry. Balloon-injured segments secreted significantly more 72- and 95-kD gelatinase than did paired distal segments at all time points. Release of both gelatinase activities was increased at 3 and 7 days relative to segments from uninjured arteries but declined again by 21 days after balloon injury. Similar results were found for gelatinase levels in extracts of arterial tissue. Consistent with the protein secretion data, in situ hybridization demonstrated that the mRNAs for both gelatinases were upregulated after balloon injury. Expression was prominent in medial smooth muscle cells, particularly around foci of necrosis, and in neointimal cells 3 and 7 days after balloon injury; 72-kD gelatinase mRNA persisted after 21 days and was prominent in regrown endothelial cells. The upregulation of gelatinase activity paralleled the time course of smooth muscle cell migration and proliferation in this model. We conclude that increased gelatinase production occurs in response to balloon injury and may play a role in permitting migration and proliferation of vascular smooth muscle cells.

Kinetics of smooth muscle cell proliferation and intimal thickening in a pig carotid model of balloon injury.

Restenosis as a result of neointimal smooth muscle cell accumulation is an important limitation to the effectiveness of balloon angioplasty as a treatment for end-stage atherosclerosis. Quantitative animal models allow the definition of pathophysiological mechanisms and the evaluation of new therapeutic strategies. In this study we quantified the time course of neointima formation by morphometry, and smooth muscle cell (SMC) proliferation by immunocytochemistry for proliferating cell nuclear antigen (PCNA), in the pig carotid artery 0-28 days following balloon injury. This led to two distinct kinds of injury observed also in clinical studies, namely medial dilatation or deep medial tearing with rupture of the internal elastic lamina. Dilatation injury alone led to medial enlargement and neointima formation by 7 days, which did not increase further up to 28 days. Medial enlargement was similar following rupture of the internal elastic lamina; however the sum of neointima formation plus the area of medial repair ('neomedia') increased progressively up to 21 days after balloon injury. Balloon injury increased the PCNA index of smooth muscle cells in the media underlying an intact internal elastic lamina maximally after 3 days. The PCNA index in the neointima and especially in the neomedia was greater and maximal after 7 days. Endothelial regrowth occurred by 21 days in the presence or absence of medial tears. Our results establish a quantitative pig model of balloon injury which will allow the assessment of new therapeutic strategies directed at two clinically relevant types of injury. Medial tearing is associated with an enhanced and localized proliferative response and may therefore be especially important in human restenosis.

The effects of exogenous nitric oxide on smooth muscle cell proliferation following porcine carotid angioplasty.

OBJECTIVES: Nitric oxide reduces platelet adhesion and platelet-thrombus formation following angioplasty and inhibits smooth muscle cell (SMC) proliferation in vitro. In this study we investigated the effects of the nitric oxide donor molsidomine on SMC proliferation and intimal growth following experimental angioplasty. METHODS: Bilateral carotid angioplasty was performed in 24 anesthetized pigs. Animals were randomized to receive oral molsidomine (whose active metabolite is SIN-1; 0.3 mg/kg every 8 h; n = 12) or placebo (n = 12) for 48 h before angioplasty and until the arteries were removed either 7 or 21 days (n = 12 each group) later. SMC proliferation was quantified by immunocytochemical staining with an antibody to the proliferating cell nuclear antigen (PCNA) and morphometric changes by computerized planimetry. SMC's were identified by alpha-actin staining. RESULTS: After 3 weeks treatment with molsidomine there was a significant prolongation in bleeding time [mean +/- SEM] (151 +/- 6 to 187 +/- 7 s. P < 0.01) and a sustained increase in arterial wall cyclic GMP (6.57 +/- 1.29 to 13.24 +/- 1.02 pmol/mg protein, P < 0.05). Molsidomine significantly reduced intimal proliferation when compared with placebo in arteries with an intact internal elastic lamina at 7 days (4.3 +/- 0.7 vs. 9.6 +/- 1.9 PCNA index, P < 0.005) and medial proliferation at 7 days (2.4 +/- 0.2 vs. 4.2 +/- 0.7 PCNA index, P < 0.05) and at 21 days (1.3 +/- 0.1 vs. 1.9 +/- 0.2 PCNA index, P < 0.05) after angioplasty. In arteries with rupture of the internal elastic lamina, intimal and medial SMC proliferation were similar in molsidomine- and placebo-treated animals. Intimal cell number and intimal area were uninfluenced by treatment with molsidomine in either the presence or absence of rupture of the internal elastic lamina. CONCLUSIONS: These results show for the first time that exogenous nitric oxide inhibits SMC proliferation following balloon angioplasty in vivo. The antiproliferative effects of nitric oxide are overwhelmed when injury is severe and are not associated with a reduction in intimal thickening. The inhibitory effects of nitric oxide on platelet adhesion and SMC proliferation identify a possible role for high local concentrations of nitric oxide to modify the vascular response to balloon angioplasty.

Abnormalities of left ventricular flow following mitral valve replacement: a colour flow Doppler study.

Left ventricular flow patterns were studied at rest by colour flow Doppler echocardiography in 33 patients with mitral tilting-disc prostheses (group 1), in 38 patients with mitral tissue prostheses (group 2) and in 18 healthy volunteers (controls). A 'crossed' flow pattern was seen in 14 patients with mechanical (42%) and in 15 patients with tissue prostheses (39%). The remaining patients and all controls had either 'parallel' or 'intermediate' flow patterns which were classified as 'normal'. There was a significant correlation between the type of flow pattern and the position of the mitral prosthesis in both study groups. The presence of a crossed flow pattern, however, was not related to functional status (assessed clinically by NYHA class) or to abnormalities on the electrocardiogram. Left atrial size was greater in patients with crossed flow than in those without, but all other echocardiographic parameters were similar. Eight patients with crossed and eight with normal flow patterns underwent treadmill exercise testing; there was no difference between the two groups with regard to exercise performance as determined by exercise duration, maximum oxygen consumption and the ventilatory response to exercise. The results of this study indicate that the pattern of blood flow within the left ventricle may be fundamentally altered by the orientation of both mechanical and tissue prostheses. The presence of a crossed flow pattern is not, however, accompanied by significant deleterious haemodynamic or functional consequences.

Amyloid, thrombosis, and acute myocardial infarction in association with a bicuspid aortic valve.

A 34 year old man presented with an inferior non-Q-wave myocardial infarction. Echocardiography showed a bicuspid aortic valve with aortic outflow obstruction. Left coronary cusp morphology was normal but the right coronary cusp was grossly distorted and replaced by a mobile echodense mass encroaching upon the aortic valve orifice. The aortic valve was replaced and pathological analysis of the excised valve showed primary amyloid infiltration of the right coronary cusp but a normal left coronary cusp. The mass adherent to the right coronary leaflet had the histological appearances of organised thrombus and this was assumed to be the source of coronary embolism. This is the first reported case of primary valvar amyloid presenting with clinical sequelae and it illustrates the need for careful clinical assessment in young patients presenting with acute ischaemic syndromes.

Tricuspid regurgitation following mitral valve replacement: an echocardiographic study.

The development of late tricuspid regurgitation following mitral valve replacement is accompanied by a severe reduction in exercise capacity and a poor functional outcome. In this study, we compared the clinical and echocardiographic characteristics of two matched groups with (n = 13) and without (n = 13) clinically significant tricuspid regurgitation. The preoperative pulmonary artery pressures and symptom durations were similar, but tricuspid regurgitation at palpation was detected only in patients who later developed severe tricuspid regurgitation (5/13 vs. 0/13; p < 0.02). None of the patients had echocardiographic evidence of rheumatic tricuspid valve disease at the time of the study, but the tricuspid annular diameter (3.7 +/- 0.5 cm vs. 3.2 +/- 0.4 cm; p < 0.05) and right ventricular diameter (4.9 +/- 0.4 cm vs. 4.0 +/- 0.8 cm; p < 0.01) were greater in patients who had developed severe late tricuspid regurgitation. Echocardiographic parameters of left ventricular function and Doppler estimated pulmonary artery systolic pressures were similar in the two groups, and no evidence of prosthetic dysfunction or aortic valve disease was found. These results imply that late tricuspid regurgitation following mitral valve replacement develops as a result of dilation of the tricuspid annulus associated with right ventricular decompensation. The persistence of uncorrected tricuspid incompetence would seem to be an important contributory factor, and its accurate detection and correction at the time of initial surgery may prove to be the most effective means of preventing the development of this important complication of mitral valve replacement.

SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty.

BACKGROUND: Nitric oxide inhibits platelet adhesion and platelet aggregation in vivo. In this study, we investigated the effects of the nitric oxide donor SIN-1 on platelet adhesion and platelet-thrombus formation following experimental angioplasty. METHODS AND RESULTS: Bilateral carotid angioplasty was performed in 20 anesthetized pigs. Animals received either SIN-1 (3-morpholino-sydnonimine; 10 micrograms/kg/min; n = 8) or placebo (n = 8) before and during angioplasty. An additional control group of pigs received trimetaphan (n = 4), which induced hemodynamic changes similar to those that followed treatment with SIN-1. Platelet deposition was quantified by the injection of autologous 111In-labeled platelets. SIN-1 reduced platelet deposition after deep arterial injury compared with placebo (mean +/- SEM, 10.870 +/- 2.415 versus 40.326 +/- 9.889 platelets x 10(6)/cm2, p < 0.05). SIN-1 reduced platelet adhesion after superficial injury compared with both placebo and trimetaphan (2.231 +/- 0.333 versus 5.278 +/- 0.606 versus 5.022 +/- 1.136 platelets x 10(6)/cm2, respectively; p < 0.005). Scanning electron microscopy confirmed that platelets were deposited in the form of an adherent monolayer following superficial endothelial denudation and were reduced in number following treatment with SIN-1. The effects of SIN-1 on platelet function were associated with a significant increase in platelet cyclic GMP concentration from baseline (3.15 +/- 0.88 versus 1.58 +/- 0.73 pmol/10(9) platelets, p < 0.005). CONCLUSIONS: SIN-1 reduces platelet adhesion and platelet-thrombus formation following experimental angioplasty. The antiadhesive effects of SIN-1 are independent of changes in systemic hemodynamics. These results imply that the administration of a nitric oxide donor may prove effective in modifying the pathophysiological response to angioplasty injury.

Late tricuspid regurgitation following mitral valve surgery.

The development of late tricuspid regurgitation is an important complication of mitral valve surgery, as it is associated with a severe impairment of exercise capacity and a poor symptomatic outcome. The pathogenesis of this condition remains poorly defined, but it is usually attributable to a functional abnormality of the tricuspid valve. Whilst its development may indicate an increased afterload on the right heart as a consequence of persistent pulmonary hypertension, mitral prosthetic dysfunction, progressive aortic valve disease or left ventricular failure, late tricuspid regurgitation may also develop in the absence of these factors and then may reflect right ventricular dysfunction and/or a localized abnormality of the tricuspid anulus. Failure to recognize and correct tricuspid regurgitation at the time of initial surgery may also account for many cases of tricuspid regurgitation but its re-appearance following tricuspid annuloplasty is uncommon and usually reflects a failure of the mitral prosthesis. A reduction in the prevalence of late tricuspid regurgitation is an important objective in view of the high operative mortality and disappointing long term results associated with reoperation for tricuspid regurgitation. This may be best achieved through combining earlier mitral valve surgery with the accurate detection and liberal correction of accompanying tricuspid incompetence at the time of initial surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Exogenous nitric oxide inhibits in vivo platelet adhesion following balloon angioplasty.

OBJECTIVES: The aim was to investigate the effects of an exogenous source of nitric oxide on in vivo platelet adhesion at the site of endothelial denudation after balloon angioplasty. METHODS: The study group consisted of 12 anaesthetised Large White pigs. Pigs were randomised to receive SIN-1 (3-morpholino-sydnonimine), an exogenous donor of nitric oxide, or placebo before and during balloon induced vessel wall injury. Platelet deposition was quantified using the injection of autologous 111indium labelled platelets. Platelet function was also monitored by the measurement of bleeding time and ex vivo whole blood aggregometry. RESULTS: Superficial vessel wall injury was confirmed histologically and platelet monolayer formation was demonstrated by scanning electron microscopy. Platelet deposition at the site of endothelial denudation was markedly reduced following SIN-1 administration compared to placebo: 1.266(SEM 0.063) v 1.732(0.060) log platelets x 10(5).cm-2, p = 0.001. SIN-1 raised platelet cyclic GMP concentration, from 4.47(2.48) to 6.14(2.44) pg.platelet-1 (p less than 0.01) and prolonged the bleeding time, from 135(5) to 202(6) s (p = 0.001), but had non-significant effects on ex vivo whole blood aggregometry. CONCLUSIONS: Exogenous nitric oxide, through the activation of platelet soluble guanylate cyclase, inhibits platelet adhesion in vivo following balloon angioplasty.

Reduced exercise capacity in patients with tricuspid regurgitation after successful mitral valve replacement for rheumatic mitral valve disease.

OBJECTIVE: To determine how severe tricuspid regurgitation influences exercise capacity and functional state in patients who have undergone successful mitral valve replacement for rheumatic mitral valve disease. DESIGN: 9 patients in whom clinically significant tricuspid regurgitation developed late after mitral valve replacement were compared with 9 patients with no clinical evidence of tricuspid regurgitation. The two groups were matched for preoperative clinical and haemodynamic variables. Patients were assessed by conventional echocardiography, Doppler echocardiography, and a maximal treadmill exercise test in which expired gas was monitored by mass spectrometry. SETTING: University Hospital of Wales, Cardiff. SUBJECTS: 18 patients who had been reviewed regularly since mitral valve replacement. MAIN OUTCOME MEASURE: Objective indices of exercise performance including exercise duration, maximal oxygen consumption, anaerobic threshold, and ventilatory response to exercise. RESULTS: Mitral valve prosthetic function was normal in all patients and estimated pulmonary artery systolic pressure and left ventricular function were similar in the two groups. Right ventricular diameter (median (range) 5.0 (4.3-5.6) v 3.7 (3.0-5.4) cm, p less than 0.01) and the incidence of paradoxical septal motion (9/9 v 3/9, p less than 0.01) were greater in the group with severe tricuspid regurgitation. Exercise performance--assessed by exercise duration (6.3 (5.0-10.7) v 12.7 (7.2-16.0) min, p less than 0.01), maximum oxygen consumption (11.2 (7.3-17.8) v 17.7 (11.8-21.4) ml min-1 kg-1, p less than 0.01), and anaerobic threshold (8.3 (4.6-11.4) v 0.7 (7.3-15.5) ml min-1 kg-1, p less than 0.05)--was significantly reduced in the group with severe tricuspid regurgitation. The ventilatory response to exercise was greater in patients with tricuspid regurgitation (minute ventilation at the same minute carbon dioxide production (41.0 (29.9-59.5) v 33.6 (26.8-39.3) l/min, p less than 0.01). CONCLUSIONS: Clinically significant tricuspid regurgitation may develop late after successful mitral valve replacement and in the absence of residual pulmonary hypertension, prosthetic dysfunction, or significant left ventricular impairment. Patients in whom severe tricuspid regurgitation developed had a considerable reduction in exercise capacity caused by an impaired cardiac output response to exercise and therefore experienced a poor functional outcome. The extent to which this was attributable to the tricuspid regurgitation itself or alternatively to the consequences of right ventricular dysfunction was not clear and requires further investigation.

Hyponatraemia secondary to an inappropriately high release of antidiuretic hormone in cardiac tamponade.

A spontaneous intrapericardial haemorrhage caused cardiac tamponade in a 29 year old paraplegic man who was being treated with warfarin. The associated persistent hyponatraemia, which was believed to be caused by an inappropriately high release of antidiuretic hormone, rapidly resolved after pericardiocentesis.