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Biomedical subjects

K Kilzer

Publications and source records attributed to K Kilzer.

18 recordsLinked to original sources

Correlation between quantitative angiographic lesion severity and myocardial contrast intensity during a continuous infusion of perfluorocarbon-containing microbubbles.

The purpose of this study was to determine whether quantitative measurements of myocardial videointensity (MVI) during continuous intravenous infusions of microbubbles could detect differences in coronary artery stenosis severity during dobutamine stress echocardiography. Coronary artery stenoses were created in seven dogs by progressively tightening a snare around the coronary artery. Intravenous infusions of perfluorocarbon microbubbles were given during dobutamine stress. The initial rate of myocardial contrast enhancement (slope), peak myocardial contrast (peak MVI) at the longest pulsing interval, and the product (slope * peak MVI) were compared as ratios in the stenosed versus adjacent normal perfusion beds. Twenty-two coronary stenoses were compared (range 16% to 80% in diameter). There was a strong correlation between both slope ratios and slope * peak MVI ratios and percent stenosis (r = -0.89 for both, p<0.001). The rate of contrast replenishment during a continuous infusion of microbubbles can be used to determine both the presence and severity of coronary stenoses during stress echocardiography.

Animals↗

Effect of significant two-vessel versus one-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging after intravenous contrast injection during dobutamine stress echocardiography.

OBJECTIVES: We sought to determine the effect of multivessel as opposed to single-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging and intravenous perfluorocarbon-exposed sonicated dextrose albumin contrast injection. BACKGROUND: Intermittent harmonic imaging has permitted the detection of myocardial perfusion abnormalities with an intravenous ultrasound contrast agent. The effect of multivessel disease on inducibility of these perfusion abnormalities is unknown. METHODS: In 10 dogs, intravenous injections of contrast agent were given at rest and during dobutamine stress echocardiography when a single coronary artery stenosis was present (> or = 50% diameter by quantitative angiography) and again when a second stenosis (range 44% to 92% diameter) was present in the vessel supplying the adjacent perfusion bed. The peak myocardial contrast was visually and quantitatively assessed in the mid and lateral regions of the perfusion bed of the first stenosis (original stenosis zone) in the presence of one- and two-vessel stenosis. RESULTS: Peak myocardial contrast defects in both the mid and lateral segments of the original stenosis zone during dobutamine stress echocardiography was significantly lower when two-vessel stenosis was present (p = 0.015), especially in the lateral segment. The spatial extent of the perfusion defect in the original stenosis zone risk area increased significantly when two-vessel stenosis was present, and correlated closely with actual risk area (r = 0.99). Previous total occlusion followed by reperfusion of the vessel supplying the original stenosis zone significantly increased the amount of collateral activity between perfusion beds. CONCLUSIONS: Collateral flow limits the spatial extent of inducible ischemia within the risk area of single-vessel stenosis. Restoring blood flow to one perfusion bed reduces the extent of a perfusion abnormality that can be induced in an adjacent stenosed bed.

Animals↗

Smaller intravenous perfluorocarbon-containing microbubbles produce greater myocardial contrast with intermittent harmonic imaging and better delineation of risk area during acute myocardial ischemia.

The purpose of this article was to determine whether applying negative or positive pressure to perfluorocarbon-containing microbubbles before intravenous injection would improve the myocardial contrast when using newer imaging techniques such as harmonic and intermittent imaging. Perfluorocarbon-containing microbubbles were exposed to sustained negative or positive pressure before intravenous injection in 10 dogs. Microbubble size distribution and concentration were measured after each exposure. Peak myocardial videointensity with intermittent harmonic imaging with each sample was compared. Microbubbles exposed to -200 mm Hg pressure before intravenous injection produced both the highest concentration of microbubbles and greater numbers of microbubbles less than 4 microns. Peak myocardial videointensity did not correlate with microbubble concentration or size but did correlate with the absolute number of microbubbles < 4 microns (mean r value 0.76, range 0.61 to 0.90). Risk area was best visualized with perfluorocarbon-containing microbubble samples containing the smallest microbubbles. We conclude that the myocardial contrast observed with perfluorocarbon-containing microbubbles can be enhanced by applying negative pressure before injection. The mechanism for this improved contrast appears to be related to creation of smaller microbubbles.

Animals↗

Myocardial perfusion abnormalities during low-dose dobutamine after coronary reperfusion can be demonstrated with intravenous perfluorocarbon-exposed sonicated dextrose albumin ultrasound contrast.

We measured background-subtracted peak myocardial videointensity (PMVI) in the left anterior descending and left circumflex perfusion zones in open-chest dogs after intravenous injection of perfluorocarbon-exposed sonicated dextrose albumin ultrasound contrast (PESDA) after reperfusion of a coronary occlusion. These measurements were repeated during low-dose dobutamine (LDD). The ratio of PMVI in the reperfused zone (RZ) compared with the adjacent normal zone (NZ) was measured at baseline and during LDD. Dogs with a >50% diameter residual stenosis were group I (n = 10), and those with <50% residual stenosis were group II (n = 13). Wall-thickening (WT) responses to LDD were not different between groups. Although the PMVI ratio (PMVI(RZ)/PMVI(NZ)) was the same in both groups at baseline, it decreased by >0.1 during LDD in 8 of 10 in group I compared with only 3 of 13 in group II dogs (p = 0.01). PMVI in the RZ increased by > or = 1.5 U in 12 of 13 group II dogs during LDD, but only in 3 of 10 group I dogs. Therefore, intravenous PESDA can be combined with WT responses to define both myocardial function and flow after reperfusion.

Adrenergic beta-Agonists↗

Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropropane-exposed sonicated dextrose albumin.

OBJECTIVES: The purpose of this study was to determine whether intravenous dextrose albumin sonicated with a commonly used gas of low blood solubility and diffusivity (perfluoropropane) could identify acute myocardial ischemia and reperfusion. BACKGROUND: Recently, it has been demonstrated that dextrose albumin sonicated with gases that have low blood solubility and diffusivity results in microbubbles capable of consistently producing myocardial ultrasound contrast after intravenous injection. It remains to be determined, however, whether this contrast agent can visually detect the myocardial blood flow abnormalities seen with acute ischemia or stunned myocardium after reperfusion. METHODS: We gave intravenous injections (0.06 ml/kg body weight) of perfluoropropane-exposed sonicated dextrose albumin to 10 open chest dogs. The measured degree of myocardial contrast (0+ to 2+) and background-subtracted peak anterior myocardial videointensity produced from each injection were measured at three stages: 1) under baseline conditions, 2) during acute ischemia produced by a proximal left anterior descending coronary artery ligation lasting 10 to 120 min, and 3) after reflow was established. Coronary blood flow was monitored during all injections by using an ultrasound flow probe placed around the left anterior descending artery. RESULTS: Coronary blood flow ranged from 0 to 137 ml/min, and peak myocardial videointensity after intravenous administration of perfluoropropane-exposed sonicated dextrose albumin ranged from 0 to 70 gray scale U. There was consistent visual myocardial opacification in all dogs during baseline conditions and a visually evident decrease in myocardial contrast in the left anterior descending artery distribution after ligation. A relative increase in contrast in this same distribution after intravenous contrast agent administration occurred in 7 of the 10 dogs during reflow. Quantitatively, there was an excellent correlation in individual dogs between peak myocardial videointensity and coronary flow at all stages (mean correlation coefficient 0.95 +/- 0.04, range 0.87 to 0.99). CONCLUSIONS: Perfluoropropane-exposed sonicated dextrose albumin is an ultrasound contrast agent that can visually identify myocardial perfusion abnormalities from a peripheral venous injection.

Acute Disease↗

Endocarditis risk of the USCI PDA umbrella for transcatheter closure of patent ductus arteriosus.

BACKGROUND: The USCI PDA Umbrella is a device to close patent ductus arteriosus (PDA) by a transcatheter technique. Human clinical trials have shown excellent efficacy in reducing or eliminating the PDA shunt, but concerns remain about the risk of infection with this device. The purpose of this study was to evaluate the risk of infection using an animal model. METHODS AND RESULTS: Susceptibility to developing endocarditis was tested by injecting a single intravenous dose of group L streptococcus. Ten piglets with a closed ductus served as controls. Two of these developed valvular vegetations. PDA was produced in 19 animals by balloon dilation of the ductus. Seven of 7 animals with PDA at the time of bacterial injection developed endarteritis of the ductus and valvular vegetations. A PDA Umbrella was placed in the remaining 12 animals, and bacteria were injected 2 weeks after device implantation. Infection was evident in the PDA Umbrella only in the single animal in which the Umbrella had embolized and been left in the left pulmonary artery. Three of the remaining 11 piglets had a significant residual leak, and all developed infection in the ductus and an additional valve. Similar to the control group, none of the animals with complete (n = 8) or nearly complete (n = 2) closure of the ductus by the PDA Umbrella had infection in or around the ductus, and only 1 had a valvular vegetation. CONCLUSIONS: In this animal model, presence of a significant PDA shunt (with or without a PDA Umbrella present) results in significantly increased susceptibility to endarteritis and endocarditis. The PDA Umbrella device does not appear to be susceptible to direct infection as early as 2 weeks after implantation if it is properly located in the ductus arteriosus. Animals with no shunt or a trivial shunt are no more susceptible to developing endocarditis 2 weeks after PDA Umbrella implantation than are controls.

Animals↗

[Abnormal origin of the ramus circumflexus sinister from the left atrium in a 30-year-old patient with aortic isthmus stenosis and atrial septal defect].

In this case report a 30-year-old woman suffering from progressive angina pectoris and dyspnea, having been operated on previously for atrial septum defect at the age of 19 and later aged 24 for coarctation of the aorta, is described. Upon observation, patient showed cardiac symptoms already under mild stress and remained resistant to nitroglycerin. Rest-ECG and serum cardiac enzymes were repeatedly without findings, while stress-ECG at a level of 100 W showed a ST-segment depression of 0.15 mV, at the same time complaining of angina pectoris symptoms. Coronary angiography revealed a left circumflex coronary artery arising from the left atrium being fully supplied by the left anterior descendent artery and the right coronary artery via pronounced collaterals, both originating from the ascending aorta. Despite such severe symptoms patient refused surgery suturing the abnormally arising artery. One year following coronary angiography patient is suffering from stabile angina pectoris without occurrence of myocardial infarction or another cardiovascular event.

Adult↗

[Coronary artery anomalies in adulthood].

In a series of 3000 consecutive coronary angiographies carried out in adults (period October 1988 through February 1991) the incidence of coronary artery anomalies was investigated. Among these there were 7.2% of patients with left-, 3.8% with right-sided and 89% with bilateral coronary artery supply. 10 cases revealed a double left anterior descendent artery (LAD), whereas in 2 patients the left circumflex artery (CX) was missing. In approximately 1% of patients origin anomalies of coronary arteries were observed, above all of the right coronary artery (RCA). A pronounced kinking of the coronaries was seen in 22 cases (11 LAD, 11 RCA) and a bridging in 2.5% of patients (74 LAD, 1 CX, 1 RCA). Of the latter, there were 21 hemodynamic active stenoses (more than 75% diameter stenosis) of which in 12 cases this narrowing was the sole cause for the heart complaints. During the same period there were 8 patients with coronary anomalies leading to shunt development out of which a 30-year-old female revealed clinically a coronary steal phenomenon. Aneurysms of the coronary arteries were observed in 54 cases (2%) whether congenital or acquired could not be ascertained. In total, there were 194 coronary anomalies in the total series (6.5%) being clinical significant in 22 cases (0.7%).

Adult↗

A new steroid-eluting epicardial lead: experience with atrial and ventricular implantation in the immature swine.

The first study with investigational steroid epicardial leads was carried out in mature canine with prototype leads. Because the demand for epicardial leads is highest in small infants and the prototype steroid-eluting lead has been redesigned, this study was carried out in immature swine to evaluate the newly designed lead. Six immature swine (2 at 5 weeks of age and 4 at 6 weeks) underwent epicardial implantation of four porous platinized tip leads: one steroid and one nonsteroid on the right atrium; one steroid and one nonsteroid on the right ventricle. At implantation, the lead terminals were connected to a percutaneous access device subcutaneously placed in the right lateral neck. This allowed chronic measurements by using an insulated needle connected with a cable to the pacing systems analyzer. Measurements were obtained at implantation and weekly for 3 weeks. Compared to the nonsteroid atrial leads, the steroid atrial leads had lower mean thresholds (P less than 0.01) at 1, 2, and 3 weeks after implantation. The mean threshold values from ventricular steroid leads were also lower and exhibited little increase from implant with the highest mean threshold of only 1.02 V, however, a statistically significant difference between steroid and nonsteroid was not reached. This newly designed steroid epicardial lead provided favorable results for continual human clinical study.

Animals↗

The influence of contrast media additives upon ventricular fibrillation thresholds during coronary angiography in ischemic and normal canine hearts.

Contrast media additives that bind calcium lower the total dose necessary to induce fibrillation. The method of measuring ventricular fibrillation threshold during coronary arteriography is sensitive and allows dose comparison at volumes relevant to clinical use. We compared two commercial formulations of sodium/meglumine diatrizoate for their effects upon fibrillation threshold in normal and ischemic dog hearts. Even though the formulations differed only by their additives, Hypaque 76 was significantly less fibrillatory than Renografin 76. This was observed at two different doses and in both ischemic and non-ischemic hearts. We conclude that amounts of additives capable of binding calcium should be kept as low as possible in sodium/meglumine diatrizoate formulations that are used for coronary angiography.

Angiocardiography↗

Contrast agents lower ventricular fibrillation threshold.

Ventricular fibrillation thresholds were measured in anesthetized, closed-chest dogs during the injection of Renografin 76 or Conray 400 into the left coronary artery. Both agents significantly lowered fibrillation threshold--Renografin to 58 +/- 7%; Conray to 20 +/- 5% of control, respectively. The experimental method estimates fibrillatory potential of contrast media more precisely than previous methods. The initial results parallel relative toxicities observed in clinical usage.

Animals↗

Intravenous perfluoropropane-exposed sonicated dextrose albumin produces myocardial ultrasound contrast that correlates with coronary blood flow.

If microbubble gas blood solubility and diffusivity are reduced, the persistence (and hence ultrasound reflectivity) of the microbubble in blood is prolonged. Recently we have sonicated a multifold dilution of human albumin with 5% dextrose while exposed to gases of low blood solubility and diffusivity and produced microbubbles that consistently opacify the myocardium after intravenous injection. The objective of this study was to test the hypothesis that a gas with very low diffusivity, perfluoropropane, when introduced into dextrose albumin during sonication, would produce visually evident myocardial ultrasound contrast after intravenous injection compared to sonicating with gases that have more rapid diffusivity. Second, we sought to determine whether the degree of contrast (peak myocardial videointensity) achieved with this agent would correlate with coronary blood flow. In eight open-chest dogs, intravenous injections of dextrose albumin sonicated with either room air, sulfur hexafluoride, or perfluoropropane (PESDA) were given under baseline conditions. PESDA injections were repeated when coronary flow was increased during low-dose dobutamine infusion. Left anterior descending coronary blood flow was monitored with transit-time flow probe. Background-subtracted anterior myocardial peak videointensity was measured after each injection. Visible myocardial opacification was seen in 100% of the 0.04 to 0.08 ml/kg intravenous injections of PESDA. No significant myocardial contrast was observed with the same doses of intravenous room air- or sulfur hexafluoride-exposed sonicated dextrose albumin. There was a strong correlation between left anterior descending coronary artery flow (range 17 to 96 ml/min) and myocardial peak videointensity (r = 0.75; p < 0.0001) in all dogs. We conclude that intravenous injections of PESDA can safely produce consistent myocardial ultrasound contrast. the peak videointensity produced correlates with changes in coronary blood flow. Therefore this agent could be used to quantify coronary blood flow noninvasively.

Air↗

Reduction in left ventricular cavitary attenuation and improvement in posterior myocardial contrast with higher molecular weight intravenous perfluorocarbon-exposed sonicated dextrose albumin microbubbles.

Although intravenous perfluoropropane-exposed sonicated dextrose albumin (C3SDA) produces myocardial contrast, the posterior myocardium cannot be visualized with epicardial or transthoracic imaging because of excessive left ventricular cavitary contrast. We hypothesized that higher molecular weight, less diffusible gases such as perfluoropentane-exposed sonicated dextrose albumin (C5SDA) would produce equivalent anterior myocardial contrast at lower intravenous doses with less cavitary attenuation. To test this hypothesis, we compared the anterior and posterior peak myocardial videointensity after 0.06 ml/kg intravenous injections of C3SDA and 0.015 to 0.030 ml/kg intravenous injections of C5SDA in seven open-chest dogs. The ability of C5SDA to detect posterior myocardial perfusion abnormalities was also tested. Despite the lower dose, intravenous C5SDA produced equivalent anterior myocardial contrast but significantly higher posterior myocardial contrast (2.6 +/- 1.9 units peak myocardial videointensity C5SDA versus 0.6 +/- 0.9 units C3SDA; p < 0.0001) because of less acoustic shadowing. The visual detection of posterior ischemia with intravenous C5SDA was also significantly improved. We conclude that increasing the molecular weight of the perfluorocarbon gas in sonicated dextrose albumin will significantly improve the detection of posterior perfusion abnormalities.

Animals↗

Detection of myocardial perfusion abnormalities during dobutamine and adenosine stress echocardiography with transient myocardial contrast imaging after minute quantities of intravenous perfluorocarbon-exposed sonicated dextrose albumin.

We have recently discovered that if ultrasound transmission is briefly suspended (triggered to just one frame per cardiac cycle) after very small doses of intravenous perfluorocarbon-exposed sonicated dextrose albumin, the myocardial contrast produced is significantly enhanced. The objective of this study was to test whether this technique (termed transient response imaging) could identify myocardial perfusion abnormalities during adenosine and dobutamine stress echocardiography. In 10 open-chest dogs with a significant (> 50%) coronary stenosis determined by quantitative angiography, intravenous perfluorocarbon-exposed sonicated dextrose albumin (0.005 to 0.01 ml/kg) was given at rest during peak dobutamine stress (20 to 30 micrograms/kg/min). Adenosine stress (100 to 140 micrograms/kg/min) was also given in seven of these dogs. The peak myocardial videointensity and spatial extent of contrast defect with transient response imaging (TRI) were compared with conventional 30 Hz frame rates, as well as wall thickening and coronary flow responses. In all 10 dogs there was visually evident myocardial contrast with TRI. In comparison, myocardial contrast was visually evident in only one of these dogs with conventional imaging. The peak myocardial videointensity ration in the stenosed perfusion bed divided by the normally perfused bed when TRI was used decreased in all dogs during dobutamine stress and correlated with minimal coronary lumen diameter (r = 0.70; p = 0.02). Visually evident myocardial contrast defects were detectable in nine of 10 dogs at peak dobutamine stress but only in one of the dogs with conventional imaging. All seven dogs that received adenosine demonstrated contrast defects with TRI, whereas none demonstrated contrast defects with conventional imaging. We conclude that the myocardial contrast produced with transient response imaging can be used to detect functionally significant coronary stenoses.

Adenosine↗

A proposed mechanism for transient increases in arterial pressure and flow during angiographic injections.

In a series of animal experiments, we have confirmed the observation that arterial pressure and flow increase distal to the injection site during power injections through non-obstructing catheters. Our data suggest that the phenomenon is secondary to the transient production of turbulence. Thus, for a given injection rate, catheters with smaller end holes create more fluid velocity, which increases the Reynolds number and causes augmentation of downstream pressure and flow. The addition of side holes decreases the fluid velocity of the injectate and minimizes the hemodynamic effects. The discussion deals with factors contributing to the generation of local turbulence, the magnitude of pressure and flow changes caused by the injections, and the clinical implications of these artifacts.

Angiography↗

Contractile reserve is maintained during the negative inotropy of coronary arteriography.

Contractile reserve was followed throughout the hemodynamic response to coronary arteriography by measuring the post-etrasystolic potentiation every tenth beat following the injection of 3 ml of Renografin-76 into the left coronary arteries of anesthetized dogs. During sinus beats, both systolic pressure and +dP/dt exhibited the usual biphasic response of negative inotropy for 5-8 seconds, followed by a rebound increase in contractility. However, the myocardium retained the ability to increase contractility following a precisely timed extrasystole. The pattern of hemodynamic response to ionic contrast agents is similar to the response of other interventions that decrease calcium inflow to the myocardial cell. Based upon differences in the electrophysiologic effects of ionic contrast agents, we speculate that excess sodium and meglumine transiently compete with calcium for external binding sites that supply calcium necessary for excitation-contraction coupling.

Animals↗

New angiographic agents with less fibrillatory propensity.

Coronary angiography with Renografin-76 (meglumine sodium diatrizoate, Squibb) lowers the ventricular fibrillation threshold (VFT) significantly and in a dose-dependent manner. Recently new contrast materials have been synthesized for possible angiographic use. We compared the fibrillatory propensities of Hexabrix (meglumine sodium ioxaglate, Guerbet), a monacid dimer; Exypaque (Nyegaard; U.S. iohexol, Winthrop), a new nonionic agent; and Amipaque (metrizamide, Winthrop), an older nonionic agent, to Renografin-76 in anesthetized dogs. The VFT following subselective left circumflex artery injections of 370-mg I and 740-mg I doses of each agent was compared to the control (no injection) threshold in 115 paired experiments in 25 dogs. At the low dose, the VFT for Renografin was significantly lower (61.8 +/- 2.3% of control threshold) than that of Hexabrix or Exypaque (69.3 +/- 2.1%, respectively; P less than 0.05). At the higher dose, the differences were more pronounced among Renografin, Hexabrix, and Exypaque (32.4 +/- 1.4%, 65.7 +/- 2.6%, and 59.2 +/- 2.4%, respectively; P less than 0.001). No statistical difference was detected between the latter two agents at these doses in nonischemic dogs. Amipaque was also less fibrillatory than Renografin and equivalent to the other two agents. These newer agents appear to offer enhanced safety for use in angiographic studies in the heart.

Angiography↗

Changes in ventricular fibrillation threshold induced by contrast agents during acute coronary artery occlusion.

In the first few hours after acute coronary thrombosis, clinical coronary angiography is associated with enhanced risk of ventricular fibrillation. In these experiments, the ventricular fibrillation threshold (VFT) was measured in anesthetized dogs before and during acute occlusion of the left circumflex coronary artery. Ischemia alone reduced the fibrillation threshold. Angiography with 1- or 2-ml does of Renografin 76 lowered VFT significantly more than did equal doses of iohexol or iopamidol. It is concluded that nonionic agents may be safer for coronary angiography in the presence of acute coronary insufficiency.

Angiography↗