Cardiovascular imaging in children and adults following Kawasaki disease.

Kawasaki disease (KD) is a paediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Two guidelines exist regarding the follow-up of patients after KD, by the American Heart Association and the Japanese Circulation Society. After the acute phase, CAA-negative patients are checked for cardiovascular risk assessment or with ECG and echocardiography until 5 years after the disease. In CAA-positive patients, monitoring includes myocardial perfusion imaging, conventional angiography and CT-angiography. However, the invasive nature and high radiation exposure do not reflect technical advances in cardiovascular imaging. Newer techniques, such as cardiac MRI, are mentioned but not directly implemented in the follow-up. Cardiac MRI can be performed to identify CAA, but also evaluate functional abnormalities, ischemia and previous myocardial infarction including adenosine stress-testing. Low-dose CT angiography can be implemented at a young age when MRI without anaesthesia is not feasible. CT calcium scoring with a very low radiation dose can be useful in risk stratification years after the disease. By incorporating newer imaging techniques, detection of CAA will be improved while reducing radiation burden and potential complications of invasive imaging modalities. Based on the current knowledge, a possible pathway to follow-up patients after KD is introduced. Key Points • Kawasaki disease is a paediatric vasculitis with coronary aneurysms as major complication. • Current guidelines include invasive, high-radiation modalities not reflecting new technical advances. • Cardiac MRI can provide information on coronary anatomy as well as cardiac function. • (Low-dose) CT-angiography and CT calcium score can also provide important information. • Current guidelines for follow-up of patients with KD need to be revised.

Pregnancy in women with a history of Kawasaki disease: management and outcomes.

OBJECTIVE: To characterise the obstetrical management and outcomes in a series of women with a history of Kawasaki disease (KD) in childhood. DESIGN: Retrospective case series. SETTING: Tertiary healthcare setting in the USA. POPULATION: Women with a history of KD in childhood. METHODS: Women completed a detailed health questionnaire and participated in research imaging studies as part of the San Diego Adult KD Collaborative Study. MAIN OUTCOME MEASURES: Obstetrical management, complications during pregnancy and delivery, and infant outcomes. RESULTS: Ten women with a history of KD in childhood carried a total of 21 pregnancies to term. There were no cardiovascular complications during labour and delivery despite important cardiovascular abnormalities in four of the ten subjects. Pregnancy was complicated by pre-eclampsia and the post-partum course was complicated by haemorrhage in one subject each. Two of the 21 progeny subsequently developed KD. CONCLUSIONS: Women with important cardiovascular sequelae from KD in childhood should be managed by a team that includes both a maternal-fetal medicine specialist and a cardiologist. Pre-pregnancy counselling should include delineation of the woman's current functional and structural cardiovascular status and appropriate adjustment of medications, but excellent outcomes are possible with appropriate care. Review of the English and Japanese literature on KD and pregnancy revealed the occurrence of myocardial infarction during pregnancy in women with missed KD and aneurysms that were not diagnosed until their acute event. Our study highlights the need for counselling with regard to the increased genetic risk of KD in offspring born to these mothers.

Modulation of pulmonary vasomotor tone in the fetus and neonate.

The high pulmonary vascular resistance (PVR) of atelectatic, hypoxic, fetal lungs limits intrauterine pulmonary blood flow (PBF) to less than 10% of combined right and left ventricular output. At birth, PVR decreases precipitously to accommodate the entire cardiac output. The present review focuses on the role of endothelium-derived nitric oxide (NO), prostacyclin, and vascular smooth muscle potassium channels in mediating the decrease in PVR that occurs at birth, and in maintaining reduced pulmonary vasomotor tone during the neonatal period. The contribution of vasodilator and vasoconstrictor modulator activity to the pathophysiology of neonatal pulmonary hypertension is also addressed.

The Internet as a source of information on breast augmentation.

The Internet was evaluated as a source of information for the layperson on the topic of breast augmentation. Three commonly used search engines (Excite, AOL, and Yahoo) were employed using the term "breast augmentation." These sites were then evaluated by each of three experienced plastic surgeons for their quality and content. Separately, 17 health Web sites were identified as authoritative by means of recommendation in lay publications. Each "supersite" was accessed, and its search engine was used. The top 10 hits for "breast augmentation" on each site were then evaluated by the senior author for content (Matthews). We found the majority of sites identified by the general search engines (AOL, Excite, Yahoo) to be physician Web sites. Forty-one unique sites were found that applied to the topic. Four of the "hits" did not actually apply to the topic. In general, the applicable Web sites contained limited but accurate procedural details and offered an interactive forum, most commonly email responses. Photographic documentation was given in less than half the sites reviewed, and most of the results shown were only "good" outcomes. Most sites did not discuss any complications of surgical procedures, but those that did were usually accurate. Eighty-three percent of the sites were biased toward a particular surgical technique. The reviewers believe that only about 15 percent of the sites were acceptable to recommend to their patients. The senior author accessed 17 Web sites that are considered authoritative health information Web sites. Each of these sites was searched for information on breast augmentation by means of its internal search engine. Only 29 percent (5 of 17) had any information in their top 10 hits. Three sites had only chat transcripts. One site had limited but accurate information with a link to the American Society of Plastic Surgeons, and one site had scientific information on product safety. No site met the criteria of accurate, complete information on the surgical procedure of breast augmentation. This study demonstrates that it is difficult for the average layperson to get authoritative information quickly and easily on at least one aspect of cosmetic surgery.

Multiple Ca(2+)-dependent modulators mediate alkalosis-induced vasodilation in newborn piglet lungs.

We previously found that alkalosis-induced vasodilation was mediated by endothelium-derived nitric oxide (EDNO) in newborn piglet pulmonary artery and vein rings precontracted with the thromboxane mimetic U-46619. In contrast, prostacyclin or K(+) channel activation contributed to the response in other preparations. This study was undertaken to determine whether EDNO alone also mediates alkalosis-induced pulmonary vasodilation in piglet lungs vasoconstricted with hypoxia and, if not, to identify the mediator(s) involved. Responses to alkalosis were measured during hypoxia under control conditions after blocking nitric oxide synthase (N(omega)-nitro-L-arginine), cyclooxygenase (meclofenamate), or both endothelium-derived modulators (Dual); after blocking voltage-dependent (4-aminopyridine), ATP- dependent (glibenclamide), or Ca(2+)-dependent K(+) (K(Ca); tetraethylammonium) K(+) channels; and after blocking both endothelium-derived modulators and K(Ca) channels (Triple). Vasodilator responses measured after 20 min of alkalosis were blunted in Dual and tetraethylammonium lungs and abolished in Triple lungs. Thus alkalosis-induced vasodilation in hypoxic lungs appeared to be mediated by three Ca(2+)-dependent modulators: EDNO, prostacyclin, and K(Ca) channels. In addition, a transient, unidentified modulator contributed to the nadir of the vasodilator response measured at 10 min of alkalosis. Future studies are needed to identify factors that contribute to the discordance between isolated vessels and whole lungs.

Stability of dopamine and epinephrine solutions up to 84 hours.

OBJECTIVES: The current practice of preparing fresh dopamine and epinephrine solutions every 24 hrs may lead to hemodynamic instability caused by the interruption of infusions with each change. We determined the stability of these catecholamines over an 84-hr period and whether stability was enhanced by dextrose-containing solutions. SETTING: Tertiary care teaching hospital. DESIGN: The stability of dopamine and epinephrine, each at three commonly used concentrations, was studied in three vehicles (10 gm/dl dextrose in water [D10W], 5 gm/dl dextrose in water [D5W], and 0.9% NaCl in water [NS]). To mimic clinical conditions, solutions were placed on syringe pumps infusing continuously into a closed system at ambient temperature for 84 hrs. MEASUREMENTS: Concentrations of dopamine in mg/ml and epinephrine in microg/ml were measured by high-performance liquid chromatography at 0, 24, 36, 48, 72, and 84 hrs. RESULTS: Dopamine and epinephrine concentrations did not change over the 84-hr period regardless of the vehicles in which the drugs were prepared. CONCLUSIONS: Clinically relevant concentrations of dopamine and epinephrine remain stable in dextrose- and saline-containing solutions for >or=84 hrs. These data suggest that solutions of these catecholamines may safely be used in clinical practice beyond the currently recommended 24 hrs.

Endothelium-independent and -dependent vasodilation in alkalotic and acidotic piglet lungs.

Although significant pulmonary hypertension can occur in patients treated with either hypocapnic alkalosis or "permissive" hypercapnic acidosis, the effects of sustained alkalosis or acidosis on subsequent vasodilator responses have not been established. This study measured the effects of 60-100 min of sustained alkalosis or acidosis on endothelium-independent and -dependent vasodilation with inhaled nitric oxide (iNO) and acetylcholine (ACh) in isolated lungs from 1-week-old piglets. After stabilization, lungs were divided into control (pH 7.40, PaCO(2) 40 torr, n = 5), alkalotic (pH 7.60, PaCO(2) 25 torr, n = 6), or acidotic (pH 7.25, PaCO(2) 65 torr, n = 5) groups and ventilated with 21% O(2) for 40 min. Acute hypoxic pulmonary vasoconstriction (HPV) was then induced with 4-6% O(2). After a stable pressor response had occurred (approximately 20 min), pulmonary artery dose-response relationships to increasing concentrations of iNO were measured. The iNO was then stopped and after a stable hypoxic pressure had again been reestablished (approximately 20 min), dose-responses to increasing concentrations of ACh were measured. Hypoxic pulmonary vascular resistance (PVR) was similar in all groups. Pulmonary artery pressure dose-response relationships to iNO and ACh were blunted in the alkalosis group, suggesting that both endothelium-independent and -dependent vasodilation were reduced during sustained hypocapnic alkalosis. In contrast, sustained acidosis did not alter subsequent vasodilator responses. Future studies must elucidate the mechanisms underlying blunted pulmonary vasodilation during sustained alkalosis and examine the consequences of sustained alkalosis therapy on subsequent vasodilator responses in clinical practice.

Mediators of alkalosis-induced relaxation of piglet pulmonary veins.

Pulmonary venous constriction leads to significant pulmonary hypertension and increased edema formation in several models using newborns. Although alkalosis is widely used in treating neonatal and pediatric pulmonary hypertension, its effects on pulmonary venous tone have not previously been directly measured. This study sought to determine whether alkalosis caused pulmonary venous relaxation and, if so, to identify the mediator(s) involved. Pulmonary venous rings (500-microm external diameter) were isolated from 1-wk-old piglets and precontracted with the thromboxane mimetic U-46619. Responses to hypocapnic alkalosis were then measured under control conditions after inhibition of endothelium-derived modulator activity or K(+) channels. In control rings, alkalosis caused a 34.4 +/- 4.8% decrease in the U-46619-induced contraction. This relaxation was significantly blunted in rings without functional endothelium and in rings treated with nitric oxide synthase or guanylate cyclase inhibitors. However, neither cyclooxygenase inhibition nor voltage-dependent, calcium-dependent, or ATP-dependent K(+)-channel inhibitors altered alkalosis-induced relaxation. These data suggest that alkalosis caused significant dilation of piglet pulmonary veins that was mediated by the nitric oxide-cGMP pathway.

Site-specific effect of guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition in isolated lamb lungs.

OBJECTIVE: To determine the effect of combining inhaled nitric oxide (NO) with an inhibitor of guanosine 3',5'-cyclic monophosphate-specific phosphodiesterase on total and segmental lung resistances. STUDY DESIGN: A controlled laboratory study in isolated blood-perfused lungs prepared from lambs. SETTING: Animal research facility affiliated with a university teaching hospital. SUBJECTS: Five newborn lambs at <48 hrs of life. INTERVENTIONS: Isolated blood-perfused lungs were prepared and treated with indomethacin (40 microg/mL) to inhibit prostaglandin synthesis. After a baseline period of normoxia (28% oxygen), pulmonary hypertension was induced with the thromboxane mimetic U46619 (0.1-0.4 microg/kg/min). During pulmonary hypertension, lungs were studied with inhaled NO only, with infusion of zaprinast only (0.25 mg/kg bolus and 0.05 mg/kg/min infusion), and with a combination of the two. For each study condition, the total pressure decrease across the lung was measured, and the inflow-outflow occlusion technique was used to partition the total pressure gradient measured at constant flow (100 mL/kg/min) into gradients across relatively noncompliant large arteries and veins and more compliant small arteries and veins. MEASUREMENTS AND MAIN RESULTS: U46619 infusion produced significant pulmonary vasoconstriction. The combination of inhaled NO and zaprinast decreased the total pressure decrease across the lung significantly more than NO alone. This effect was primarily attributable to a significantly greater decrease in gradient across the small artery segment after inhaled NO and zaprinast compared with NO alone. CONCLUSIONS: Guanosine 3',5'-cyclic monophosphate phosphodiesterase inhibition with zaprinast enhances the effect of inhaled NO, particularly in conditions in which small arteries represent the site of resistance. Phosphodiesterase inhibition may be a promising adjunct to inhaled NO for the treatment of persistent pulmonary hypertension.

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Discordant effects of alkalosis on elevated pulmonary vascular resistance and vascular reactivity in lamb lungs.

OBJECTIVES: After an initial vasodilator response to alkalosis, many children with pulmonary hypertension exhibit marked pulmonary vascular reactivity despite continued alkalosis therapy. This study sought to a) identify the mediator of alkalosis-induced pulmonary vasodilation in isolated lamb lungs; b) determine whether alkalosis-induced pulmonary vasodilation decreases over time in this model; and c) determine whether alkalosis enhanced vascular reactivity to subsequent pressor stimuli. DESIGN: Prospective, interventional study. SUBJECTS: Isolated perfused lungs from 1-month-old lambs. INTERVENTIONS: Hypocarbic alkalosis, hypoxia, and infusion of the thromboxane mimetic agent U46619 MEASUREMENTS AND MAIN RESULTS: Pulmonary artery pressure was measured at constant flow, so a change in pressure reflects change in resistance. Hypoxic pulmonary artery pressure was compared after 20 and 100 mins of hypocarbic alkalosis or normocarbia in control and cyclooxygenase-inhibited lungs. Pulmonary artery dose responses to U46619 were then measured in control lungs. Responses to hypoxia and U46619 were also compared after 60-80 mins of hypocarbic or normocarbic normoxia. Hypocarbic alkalosis acutely reduced hypoxic pulmonary vascular resistance, and this was sustained for at least 100 mins. Cyclooxygenase inhibition blocked this vasodilation, suggesting that it was mediated by dilator prostaglandins. However, subsequent reactivity to U46619 was enhanced in hypoxic alkalotic lungs, and both hypoxia and U46619 caused significant vasoconstriction in normoxic alkalotic lungs. CONCLUSIONS: Alkalosis caused sustained vasodilation when pulmonary vascular resistance was high but either failed to attenuate or enhanced vascular reactivity to subsequent pressor stimuli.

Maturational changes in ovine pulmonary vascular responses to inhaled nitric oxide.

Developmental changes in modulation of pulmonary vasomotor tone by endothelium-derived nitric oxide (EDNO) may reflect maturational differences in endothelial synthesis of and/or vascular smooth muscle response to nitric oxide. This study sought to determine whether pulmonary vascular sensitivity and responsiveness to nitric oxide change during newborn development, and whether this is related to changes in guanylate cyclase activity. Pulmonary artery dose-responses to inhaled nitric oxide (iNO, 0.25-100 parts per million) were measured in hypoxic, indomethacin-treated, isolated lungs from 1-day (1-d)- and 1-month (1-m)-old lambs. The lungs of 1-m-old lambs were ventilated with 4% (oxygen) O2, and lungs of 1-d-old lambs were ventilated with either 4% or 7% O2 in order to achieve similar stimuli or vasomotor tone. Cyclic guanosine monophosphate (cGMP) concentrations in the perfusate were measured at iNO concentrations of 0, 5, and 100 parts per million (ppm). Basal and stimulated pulmonary guanylate cyclase activity was also measured in lung extracts in vitro. The effects of iNO were similar in both 1-d groups, even though baseline hypoxic tone was significantly higher in 1-d lungs ventilated with 4% O2 than with 7% O2. Furthermore, both the 1-d 7% O2 and 1-d 4% O2 lungs exhibited greater responsiveness and sensitivity to iNO than 1-m lungs. Perfusate cGMP concentrations and soluble guanylate cyclase activity were higher under stimulated than basal conditions, but neither differed statistically between 1 d and 1 m. These data suggest that pulmonary vascular responsiveness and sensitivity to nitric oxide decrease with age, but the mechanisms underlying these maturational changes require further investigation.

Mediators of alkalosis-induced relaxation in pulmonary arteries from normoxic and chronically hypoxic piglets.

Alkalosis-induced relaxation was measured in precontracted arterial rings from 1-wk-old piglets exposed to normoxia or to 3 days of chronic hypoxia. In normoxic piglet arteries, alkalosis-induced relaxation was blunted in arteries without functional endothelium and in arteries treated with nitric oxide synthase or guanylate cyclase inhibitors but not in arteries treated with cyclooxygenase inhibitors or Ca2+- and ATP-dependent K+-channel inhibitors. Inhibition of voltage-dependent K+ channels with 10(-3) M 4-aminopyridine also failed to block alkalosis-induced relaxation. 4-Aminopyridine at 10(-2) M did block the response, but this may have been due to sustained vascular smooth muscle depolarization. Arteries from hypoxic piglets exhibited greater contraction to the thromboxane mimetic U-46619, decreased endothelium-dependent relaxation, and blunted alkalosis-induced relaxation. The residual relaxation was eliminated by nitric oxide synthase but not by cyclooxygenase or voltage-dependent K+-channel inhibition. Alkalosis-induced relaxation of newborn piglet pulmonary arteries appears to be mediated by the nitric oxide-cGMP pathway and is attenuated after 3 days of hypoxia, likely because of decreased nitric oxide activity.

Developmental changes in synthesis of and responsiveness to prostaglandins I2 and E2 in hypoxic lamb lungs.

Previous studies have shown that the attenuated hypoxic pulmonary vasoconstriction (HPV) of young newborn lamb lungs was enhanced by cyclooxygenase inhibition. We sought to determine whether this reflected greater synthesis of and (or) responsiveness to dilator prostaglandins (PG). Protocol 1 measured responses to graded hypoxia and perfusate concentrations of 6-keto-PGF1alpha (the stable metabolite of PGI2) and PGE2 in isolated lungs from 1-day- and 1-month-old lambs. Protocol 2 compared dose responses and segmental vascular resistances during infusion of PGI2 and PGE2 in hypoxic, cyclooxygenase-inhibited, lungs from 1- to 2-day-old and 1- to 3-month-old lambs. Lungs of 1-day-old lambs with attenuated responses to 4% O2 had significantly higher perfusate concentrations of 6-keto-PGF1alpha and PGE2, but responses to both PGE2 and the more potent vasodilator, PGI2 did not differ with age. These data support the hypothesis that attenuated HPV in young newborn lamb lungs is due to increased synthesis of dilator PG, particularly PGI2.

Relative effects of cyclooxygenase and nitric oxide synthase inhibition on vascular resistances in neonatal lamb lungs.

Effective attenuation of pulmonary vasoconstriction is essential during early postnatal development when increased pulmonary vascular resistance (PVR) may lead to a resumption of right-to-left shunting across fetal channels. In addition, modulation of venous resistance contributes to normal lung fluid balance. This study was designed to identify the relative modulating effects of endothelium-derived nitric oxide (EDNO) and dilator prostaglandins (PG) on normoxic and hypoxic pulmonary vasomotor tone in young newborns. Total and segmental PVR were measured using inflow-outflow and double occlusion techniques in isolated lungs of 6-h-old lambs studied under control conditions or after blocking PG and/or EDNO synthesis with indomethacin and/or N omega-nitro-L-arginine, respectively. During normoxia, both indomethacin and N omega-nitro-L-arginine were required to increase total PVR, but EDNO appeared to have the greater modulating effect. Indomethacin markedly enhanced hypoxic pulmonary vasoconstriction of large and small arteries and small veins, whereas N omega-nitro-L-arginine caused a lesser, but significant, increase in hypoxic pulmonary vasoconstriction of small arteries and veins, suggesting that dilator PG played the dominant modulating role during hypoxia. In addition, PG synthesis appeared to be enhanced after inhibition of EDNO synthesis. In contrast, indomethacin caused a decrease in venous resistance, suggesting that constrictor prostanoids had a greater effect than dilator PG on this segment. EDNO had a modest modulating effect on venous resistance in these lungs. These data suggest that dilator PG and EDNO exert complementary effects in attenuating total and segmental PVR during normoxia and hypoxia in 6-hold lamb lungs.

Detection of bacteriocins of lactic acid bacteria isolated from foods and comparison with pediocin and nisin.

A total of 663,533 colonies from 72 dairy and meat sources showed a detection rate of 0.2% for bacteriocin producers using direct plating techniques. A further 83,000 colonies from 40 fish and vegetable sources showed a detection rate of 3.4% for bacteriocin producers using selective enrichment procedures. A collection of seven purified isolates showing a different host spectrum of bacteriocin activity and with the ability to produce bacteriocins in broth culture were compared with nisin and pediocin (with respect to their inhibitory activity, determined by the critical dilution method), against various indicator bacteria in agar and broth. The sensitivity of Listeria species to various bacteriocins was influenced by the agar and broth test systems used. A Lactobacillus curvatus strain was found to be the most suitable indicator for quantitating antimicrobial effects of all the bacteriocins investigated in both agar and broth test systems. The bacteriocin-producing isolates were characterized by biochemical reactions and DNA restriction enzyme profiles and taxonomic identification revealed species of Lactobacillus, Carnobacterium and Lactococcus assigned on the basis of 16S rDNA sequences.

Left ventricular assist device support of medically unresponsive pulmonary hypertension and aortic insufficiency.

Most centers consider medically unresponsive pulmonary hypertension an absolute contraindication to orthotopic cardiac transplantation because the alternative surgical therapy, heterotopic graft placement, is associated with decreased survival, although most patients normalize their pulmonary hemodynamics postoperatively. Orthotopic transplantation in patients with elevated, but responsive pulmonary pressures, also is associated with an increased operative mortality rate and decreased long-term survival. The authors present the case of a patient with medically unresponsive pulmonary hypertension who was mechanically supported in an effort to improve his orthotopic transplant candidacy and decrease his risk. After informed consent, a HeartMate left ventricular assist device (LVAD) was inserted and the pulmonary hemodynamic response was monitored. Immediately before LVAD insertion, the pulmonary artery pressure (PA) was 74/28 mmHg with a transpulmonary gradient (TPG) of 28 mmHg, and a pulmonary vascular resistance (PVR) of 6.6 Wood units, despite prolonged dobutamine, milrinone, and prostaglandin E1 infusions. After 10 weeks of LVAD support, pressure and resistance improved; pulmonary artery pressure was 28/15 mmHg, transpulmonary gradient was 15 mmHg, and pulmonary vascular resistance was 2.8 Wood units. This patient subsequently underwent an uneventful orthotopic heart transplant. At 1 year after transplantation, pulmonary artery hemodynamics were normal (PA 34/14 mmHg, TPG at 8 mmHg, and PVR at 1.5 Wood units). The authors recommend the consideration of LVAD placement in patients with medically unresponsive pulmonary artery hypertension to assess PA responsiveness and improve the patient's orthotopic cardiac transplant candidacy and decrease the operative risk. However, several weeks may be needed for normalization of pressure and resistance.

Incorporation of nisin in micro-particles of calcium alginate.

Nisin was successfully incorporated into a matrix of calcium alginate and ground into micro-particles smaller than 150 microns. Formation of micro-particles and incorporation of nisin was verified by scanning electron microscopy and by the reduction in the inactivation of nisin activity with proteolytic enzymes. Incorporation efficiency was 87-93% and the nisin in the alginate-incorporated form was 100% active against an indicator culture of Lactobacillus curvatus both in MRS broth and reconstituted skim milk.