Developing a transcatheter injectable nanoclay- alginate gel for minimally invasive procedures.

Shear-thinning materials have held considerable promise as embolic agents due to their capability of transition between solid and liquid state. In this study, a laponite nanoclay (NC)/alginate gel embolic agent was developed, characterized, and studied for transcatheter based minimally invasive procedures. Both NC and alginate are biocompatible and FDA-approved. Due to electrostatic interactions, the NC/alginate gels exhibit shear-thinning properties that are desirable for transcatheter delivery. The unique shear-thinning nature of the NC/alginate gel allows it to function as a fluid-like substance during transcatheter delivery and as a solid-like embolic agent once deployed. To ensure optimal performance and safety in clinical applications, the rheological characteristics were thoroughly investigated to optimize the mechanical properties of the NC/alginate gel, including storage modulus, yield stress/strain, and thixotropy. To improve physicians' experience and enhance the predictability of gel delivery, a combination of experimental and theoretical approaches was used to assess the injection force required for successful delivery of the gel through clinically employed catheters. Overall, NC/alginate gel exhibited excellent stability and tunable injectability by optimizing the composition of each component. These findings highlight the gel's potential as a robust embolic agent for a wide range of minimally invasive procedures.

Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics.

Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.

Experimental and Simulation Studies on Nonwoven Polypropylene-Nitrile Rubber Blend: Recycling of Medical Face Masks to an Engineering Product.

The battle against the COVID-19 pandemic counters the waste management system, as billions of single-use face masks are used per day all over the world. Proper disposal of used face masks without jeopardizing the health and the environment is a challenge. Herein, a novel method for recycling of medical face masks has been studied. This method incorporates the nonwoven polypropylene (PP) fiber, which is taken off from the mask after disinfecting it, with acrylonitrile butadiene rubber (NBR) using maleic anhydride as the compatibilizer, which results in a PP-NBR blend with a high percentage economy. The PP-NBR blends show enhanced thermomechanical properties among which, 70 wt % PP content shows superior properties compared to other composites with 40, 50, and 60 wt % of PP. The fully Atomistic simulation of PP-NBR blend with compatibilizer shows an improved tensile and barrier properties, which is in good agreement with the experimental studies. The molecular dynamics simulation confirms that the compatibility between non-polar PP and polar NBR phases are vitally important for increasing the interfacial adhesion and impeding the phase separation.

New insights into the mechanism of neurally mediated syncope.

OBJECTIVE: To determine the role of the cerebral cortex in neurally mediated syncope, the electroencephalograms (EEG) of patients recorded during head up tilt table test were analysed. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: 18 patients with syncope or near syncope underwent head up tilt table test with simultaneous ECG and EEG monitoring. METHODS: Standard 70 degrees tilt table test was done with simultaneous ECG and EEG monitoring. EEG waveforms were analysed by both visual inspection and spectral analysis. RESULTS: 6 of 18 patients (33%) had a positive tilt table test. Before syncope slow waves increased in patients with a positive test. In addition, five of six tilt positive patients (83%) had slow wave activity that lateralised to the left side of the brain (mean (SD) 822 (724) v 172 (215) micro V(2), p < 0.05), while none of the tilt negative patients exhibited lateralisation (24 (15) v 26 (19) micro V(2), NS). Spectral analysis showed that the lateralisation occurred in the delta frequency. The lateralisation preceded the event by 5-56 seconds (18 (21) seconds). CONCLUSIONS: EEG activity lateralises to the left hemisphere of the brain before syncope. The lateralisation precedes syncope and is associated with the onset of bradycardia, hypotension, and clinical symptoms. These findings suggest that the central nervous system may have a role in neurally mediated syncope.

Electrophysiologic basis by which epinephrine facilitates defibrillation after prolonged episodes of ventricular fibrillation.

STUDY OBJECTIVE: Even though epinephrine has been shown to decrease the electrical stability of the heart, it is used extensively in cardiac resuscitation. The objective of this study is to document electrophysiologic parameters of epinephrine, which would facilitate defibrillation. METHODS: In 20 swine, electrically induced ventricular fibrillation was allowed to continue for 10 minutes. Animals were then randomly assigned to receive either intracardiac injection of 1 mg of epinephrine or 10 mL of normal saline solution. Synchronization and dispersion of the repolarization of fibrillatory waves and cycle length were measured. RESULTS: As the ventricular fibrillation continued, cycle length was prolonged, and synchronization and dispersion deteriorated. With epinephrine, cycle length shortened from 416+/-21 to 204+/-23 ms (P<.005), synchronization improved from 114+/-13 to 61+/-10 ms (P<.05), and dispersion narrowed from 84+/-10 to 49+/-8 ms (P<.005). Normal saline solution had no effect. Successful resuscitation was achieved in all 10 animals administered epinephrine and only 1 animal in the saline solution group. CONCLUSION: Epinephrine's effect on cycle length, synchronization, and dispersion of repolarization of fibrillatory waves may be the mechanism with which it facilitates defibrillation.

Atheromatous plaque reflects serum total cholesterol levels: a comparative morphologic study of endarterectomy coronary atherosclerotic plaques removed from patients from the southern part of India and Caucasians from Ottawa, Canada.

BACKGROUND: Natives of South India have a very high incidence of coronary artery disease, despite low calorie and fat intake. HYPOTHESIS: This study was undertaken to determine whether morphologic features of atheromatous plaque reflect the serum total cholesterol. METHODS: Fifty-three endarterectomy specimens from patients (mean age 47 +/- 9 years, mean cholesterol 203 +/- 47 mg/dl) obtained from one cardiac surgeon working in a single institution in South India were evaluated. Morphologic findings were compared with 40 endoarterectomy specimens obtained from age-matched Caucasians from Ottawa, Canada, with a reported mean cholesterol of 262 +/- 47 mg/dl. Morphometric measurements of the vessel size, percent stenosis, and the various components of the atherosclerotic plaque were determined by computerized planimetry. RESULTS: The vessel size was smaller in the Indian than in the Canadian population (4.6 +/- 2.9 vs. 5.6 +/- 3.0 mm2, p = 0.07), the plaque area was less (4.3 +/- 2.3 vs. 5.3 +/- 2.8 mm2, p = 0.055) and the calculated percent stenosis was significantly less (93 vs. 96%, p = 0.028). Of all the parameters evaluated, only necrotic core in the Indian population (7.1 +/- 10.9% vs. Canadian 16.7 +/- 19.7%, p < 0.001) and proteoglycan deposition (7.9 +/- 11.2% vs. Canadian 3.7 +/- 5.3%, p < 0.023) were significantly different. Despite the Indians having low total cholesterol, there was greater diffuse double and triple-vessel disease and at a younger age than in the Caucasians. CONCLUSIONS: From our data, it appears that the mechanism of development of atherosclerotic disease in the Indians may be different because they have smaller vessels, smaller necrotic core, and greater proteoglycan deposition. Other etiologies, especially those related to a high carbohydrate diet (which is typical for South Indians), should be considered.

Role of dietary magnesium deficiency in the pressor and arrhythmogenic response to epinephrine in the intact dog.

The effect of dietary magnesium deficiency on the pressor and arrhythmogenic responses to epinephrine was investigated in 19 dogs maintained either on a normal diet (11 dogs) or a diet deficient in magnesium (8 dogs). Magnesium-deficient dogs had significantly lower serum magnesium levels than the control dogs on a normal diet. Magnesium-deficient dogs showed an increased pressor sensitivity to epinephrine as determined by the dose of epinephrine required to cause a maximal pressor response (3.4 micrograms/kg/min compared to 13.4 micrograms/kg/min, p < 0.05). Magnesium-deficient dogs also had a significantly lower threshold dose for ventricular premature beats (0.8 microgram/kg/min compared to 2.7 micrograms/kg/min, p < 0.05). Acute administration of magnesium sulfate restored pressor sensitivity and ventricular premature beat threshold to normal levels in the magnesium-deficient dogs. Threshold dose for ventricular tachycardia beat was similar in both normal and magnesium-deficient dogs, and threshold was raised significantly in both groups by acute administration of magnesium.

Cerebral ischemia and reperfusion: prevention of brain mitochondrial injury by lidoflazine.

Mitochondrial degradation is implicated in the irreversible cell damage that can occur during cerebral ischemia and reperfusion. In this study, the effects of 10 min of ventricular fibrillation and 100 min of spontaneous circulation on brain mitochondrial function was studied in dogs in the absence and presence of pretreatment with the Ca2+ antagonist lidoflazine. Twenty-three beagles were separated into four experimental groups: (i) nonischemic controls (ii) those undergoing 10-min ventricular fibrillation, (iii) those undergoing 10-min ventricular fibrillation pretreated with 1 mg/kg lidoflazine i.v., and (iv) those undergoing 10-min ventricular fibrillation followed by spontaneous circulation for 100 min. Brain mitochondria were isolated and tested for their ability to respire and accumulate calcium in a physiological test medium. There was a 35% decrease in the rate of phosphorylating respiration (ATP production) following 10 min of complete cerebral ischemia. Those animals pretreated with lidoflazine showed significantly less decline in phosphorylating respiration (16%) when compared with nontreated dogs. Resting and uncoupled respiration also declined following 10 min of fibrillatory arrest. One hundred minutes of spontaneous circulation following 10 min of ventricular fibrillation and 3 min of open-chest cardiac massage provided complete recovery of normal mitochondrial respiration. Energy-dependent Ca2+ accumulation by isolated brain mitochondria was unimpaired by 10 min of complete cerebral ischemia. However, by 100 min after resuscitation, there was a small, but significant rise in the capacity for mitochondrial Ca2+ sequestration when compared to either control or fibrillated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent early ischemic events after thrombolysis for acute myocardial infarction.

Myocardium salvaged by early thrombolysis and then perfused through a residual stenosis may be at risk for ischemic events. To investigate this possibility, the short-term (2-week) clinical course of 81 consecutive patients managed within a randomized intracoronary thrombolysis trial was reviewed. All patients underwent coronary angiography within 5 hours of symptoms of acute myocardial infarction and were stratified into the following 3 outcome groups: patients with initially subtotal occlusion (subtotal group, n = 17), those with initial total occlusion and infarct artery reperfusion (reperfused group, n = 24) and those with continued infarct artery occlusion (occluded group, n = 40). Recurrent ischemic events were defined as spontaneous typical angina, provokable angina on predischarge exercise testing, and reinfarction. Eleven of 17 patients (65%) in the subtotal and 11 of 23 patients (48%) in the reperfused groups had an ischemic event (difference not significant). In contrast, 4 of 37 patients (11%) with occlusion had an ischemic event (p less than 0.01 compared with patients in the subtotal or reperfused groups). Four patients were excluded because of early (within 72 hours) elective coronary bypass surgery or death from pump failure. To eliminate the impact of multivessel coronary artery disease (CAD), 39 patients with 1-vessel CAD were analyzed separately. Five of 9 patients (56%) in the subtotal group, 3 of 10 (30%) in the reperfused group and only 2 of 20 (10%) in the occluded group had an ischemic event. These observations suggest the need for a more definitive revascularization strategy for acute myocardial infarction.

Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise.

Although digoxin is often the first choice for control of ventricular response in chronic atrial fibrillation, it fails to slow exercise rates. Diltiazem, a calcium channel antagonist that slows atrioventricular conduction, was administered to 16 patients who failed to achieve adequate rate control on low level exercise testing despite digoxin therapy. Therapeutic response to diltiazem was assessed with submaximal and maximal exercise tests and 24 hour ambulatory electrocardiographic monitoring. During the diltiazem treatment phase, ventricular response at rest diminished (96 +/- 17 versus 69 +/- 10 beats/min, p less than 0.001) as did rate during submaximal exercise (155 +/- 28 versus 116 +/- 26, p less than 0.001), maximal exercise (163 +/- 14 versus 133 +/- 26, p less than 0.001) and average ventricular response during 24 hour monitoring (87 +/- 13 versus 69 +/- 10, p less than 0.001). Rate at rest decreased 26 +/- 15% and submaximal exercise rate diminished 24 +/- 12%. Thirteen (81%) of the 16 patients exhibited at least 15% slowing of rate at rest and during submaximal exercise. Eleven patients (69%) reported alleviation of symptoms. There was no change in serum digoxin levels during diltiazem treatment (1.3 +/- 0.5 versus 1.3 +/- 0.6 ng/ml, p = NS). On withdrawal of diltiazem, ventricular response returned to baseline values. Diltiazem is an effective agent for control of ventricular response, both at rest and during exercise, in digoxin-treated patients with chronic atrial fibrillation.

Ultrastructure and elemental composition of human pancreatic calculi.

Scanning electron microscopy (SEM) and energy dispersive x-ray fluorescence (EDXRF) have been used in this study to investigate the morphology, nature, and arrangement of major, minor, and trace elements in human pancreatic calculi (PC) obtained from patients with alcoholic and tropical pancreatitis. The present study has confirmed previous observations that PC are rich in CaCO3 (as calcite) and many other elements. Further, we have shown for the first time that the amorphous nidus contained only iron, chromium, and nickel, whereas the outer shell contained calcium and 17 other elements. Based on our studies, we postulate the formation of PC to be taking place in multilayers and multistages. Formation of inner protein nidus in the form of a cobweb is the first stage, then calcite is deposited on this fibrous network as tiny crystals. Because of their high surface area and high surface activity, other metallic ions are incorporated onto it through co-precipitation, adsorption, and/or lattice substitution. This study has further shown that irrespective of the etiology for chronic pancreatitis, the structure and composition of PC are the same suggesting a common pathway for lithogenesis in the pancreatic duct.

The influence of residual coronary stenosis on size of infarction after reperfusion in a canine preparation.

The effect of a residual coronary artery stenosis on size of myocardial infarction was studied in an open-chest canine preparation of coronary occlusion and reperfusion. Eighteen male mongrel dogs (16 to 26 kg) underwent left thoracotomy under general anesthesia; the circumflex artery was instrumented with a hydraulic cuff occluder, a screw clamp, and an electromagnetic flow probe. Animals were randomized to one of three groups: group I (n = 6) had a 6 hr circumflex occlusion, group II (n = 6) had a 2 hr occlusion followed by 4 hr of partial reperfusion through a residual stenosis adjusted to approximately 30% of baseline flow, and group III (n = 6) had full reperfusion for 4 hr after a 2 hr occlusion. Zones of risk, infarction, and no reflow were defined by staining with Evans blue, triphenyl tetrazolium chloride, and fluorescein, respectively. At 6 hr the hearts were excised and areas of risk, infarction, no reflow, and hemorrhage were determined by planimetry of serial transverse heart slices (5 mm thick). Infarction as a percent of the risk area was 96 +/- 1% in group I, 90 +/- 2% in group II, and 79 +/- 4% in group III (p less than .001), and the differences between each of the groups were significant. Gross hemorrhage was seen in none of the six dogs in group I, two of the six in group II, and five of the six in group III, but did not affect infarct size. We conclude that residual stenoses may exert a deleterious effect on the outcome of coronary reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent and interactive effects of digoxin and quinidine on the atrial fibrillation threshold in dogs.

To assess the effects of digoxin as single therapy and in combination with quinidine in the treatment of atrial fibrillation, the atrial fibrillation threshold was determined from the right atrial appendage and Bachmann's bundle in 11 open chest dogs. In group 1 (six dogs), the atrial fibrillation threshold was determined at baseline, post-quinidine (10 mg/kg intravenously) and then post-digoxin (50 micrograms/kg intravenously). In group 2 (five dogs), the order of drug administration was reversed. The results of this study were: 1) Digoxin had no significant effect on the atrial fibrillation threshold when given alone. 2) Quinidine significantly increased the atrial fibrillation threshold (p less than 0.002) and the addition of digoxin resulted in a further increase in threshold (p less than 0.002). 3) Quinidine produced greater suppression of atrial fibrillation induction at the right atrial site than at the Bachmann's bundle site, suggesting differential effects of quinidine on atrial fibers.

Arteriographic predictors of spontaneous improvement in left ventricular function after myocardial infarction.

To better characterize the changes in left ventricular ejection fraction after myocardial infarction, we compared radionuclide ventriculograms obtained acutely and 2 weeks after acute myocardial infarction in 40 patients. These patients underwent angiography within a mean of 4 hr and 20 min after the onset of symptoms of infarction and either received no therapy (32 patients who were control subjects in a thrombolysis trial) or did not experience reperfusion (eight patients) despite receiving streptokinase infusions. In all 40 patients, the change in left ventricular ejection fraction over 2 weeks was small (+2.6%). Patients were then grouped according to the presence or absence of residual flow on their angiograms. Residual flow was considered to be present in 21 patients, in 12 by virtue of subtotal occlusion of the artery supplying the area of infarct and in nine because of well-developed coronary collaterals to the distal infarct artery. Mean change in ejection fraction for patients with residual flow was +6.9 +/- 2.3% vs -2.2 +/- 1.7% for patients without residual flow (p less than .01). Fourteen of 21 (67%) patients with residual flow had a spontaneous rise in ejection fraction of greater than 5%, as compared with two of 19 (11%) patients without residual flow (p less than .01). Time to peak level of creatine kinase (CK) was significantly shorter in the residual flow group (15 vs 23 hr, p less than .01), while the peak level of CK was lower (1550 vs 2220 IU) in these patients. This latter difference did not reach statistical significance (p = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium deficiency and myocardial infarct size in the dog.

Although epidemiologic data suggest a relation between myocardial infarction death rates and dietary intake of magnesium, there are no experimental studies reflecting such a phenomenon. It is now reported that beagle dogs kept on a severely magnesium-deficient diet for 100 days develop a larger infarct than do control animals. Control animals were either kept on the same diet as experimental animals with supplementary magnesium, or were fed standard dog chow. The control groups were indistinguishable and were therefore pooled. Infarction was produced by occlusion of the left anterior descending coronary artery for 1 hour followed by 4 hours of reperfusion. Slices of ventricular myocardium, 5 mm thick, were made from the apex to the base. Ischemic muscle, considered to be the muscle at risk, was delineated by a microsphere-autoradiographic method, and necrotic muscle was delineated by tetrazolium stain. Involved areas were measured by planimetry, and these integrated to produce the volume. The volumes of muscle made ischemic were similar in the experimental and control groups. The volumes of necrotic muscle, however, were less in the control than in the experimental animals. The ratio of necrotic muscle volume to the volume of muscle at risk was greater in the experimental animals than in the control animals by a factor of almost two (p less than 0.004). These experiments indicate that, under the conditions used here, animals fed a magnesium-deficient diet develop a larger infarct than do control animals. This could occur either through decreased postocclusion collateral flow or increased vulnerability of the ischemic muscle in magnesium-deficient animals. Although these experiments cannot rule out an effect on postocclusion collateral flow, they do suggest that electrolyte abnormalities related to magnesium deficiency are of such a character as to increase myocardial vulnerability to injury.

Temporal evolution of the human coronary collateral circulation after myocardial infarction.

An analysis of the coronary collateral circulation in a consecutive series of 116 postinfarction angiograms from patients with persistent 100% occlusion of their infarct artery is reported. Patients were classified into four groups according to the interval between acute infarction and angiography. Of 42 patients studied within 6 hours of infarction (Group I), 52% had no evidence of any coronary collateral development as compared with only 8% (1 of 16 patients) studied 1 day to 2 weeks after infarction (Group II). Virtually all patients studied beyond 2 weeks after myocardial infarction (14 to 45 days, Group III) and later than 45 days (Group IV) had visible collateral flow. Angiographically "well developed" collateral channels were seen in only 16% of Group I patients compared with 62, 75 and 84% of patients in Groups II to IV, respectively. Of six patients studied twice, on the day of the infarction and 2 weeks later, only one patient had collateral vessels on the day of infarction, whereas all six patients did at follow-up study. Group I patients were studied as part of a randomized acute myocardial infarction reperfusion trial, whereas the other patients were referred for angiography primarily because of post-infarction ischemia. Within the limitations imposed by the patient selection process, it is concluded that well developed coronary collateral vessels are rarely present at the time of infarction. After infarction, they develop rapidly and are generally demonstrable within 2 weeks. It may also be inferred that the preservation of ischemic myocardium by well developed coronary collateral vessels at the time of myocardial infarction may be an uncommon occurrence.

Exercise radionuclide ventriculographic responses in hypertensive patients with chest pain.

The effectiveness of exercise-treadmill testing in diagnosing coronary-artery disease in hypertensive patients is limited by a high rate of false positivity. Exercise radionuclide ventriculography, however, relies on different criteria (ejection fraction and wall motion), and we have evaluated this procedure in 37 hypertensive and 109 normotensive patients with chest pain, using coronary arteriography as an indicator of coronary disease. In the hypertensive cohort there was no difference in the ejection fraction at rest between the 17 patients with coronary disease and the 20 without it. Neither group had a significant mean (+/- S.E.M.) change in ejection fraction from rest to exercise (-1.9 +/- 2 and - 1.4 +/- 1 per cent, respectively). A wall-motion abnormality developed during exercise in 5 of the 17 hypertensive patients with coronary disease (29 per cent) and in 4 of the 20 without it (20 per cent) (P = not significant). In the normotensive cohort, however, the peak-exercise ejection fractions were significantly different. The 71 patients with coronary disease had a mean decrease of 3.6 +/- 1 per cent, in contrast to the patients without coronary disease, who had an increase of 6 +/- 1 per cent (P less than 0.001). An exercise-induced wall-motion abnormality was seen in 35 of the 71 patients with coronary disease (48 per cent), as compared with 3 of the 38 without it, (8 per cent) (P less than 0.001). We conclude that exercise radionuclide ventriculography is inadequate as a screening test for coronary atherosclerosis in hypertensive patients with chest pain.